Steven M. Reppert: Difference between revisions

Steven M. Reppert
Steven M. Reppert
Born	September 4, 1946 (age 78); Sioux City, Iowa
Citizenship	United States
Alma mater	University of Nebraska, Lincoln; University of Nebraska, College of Medicine, Omaha; Harvard Medical School, Boston, Massachusetts;
Known for	Fetal circadian clock; Melatonin receptors; Circadian clock mechanism in mammals; Monarch butterfly sun compass;
	Scientific career
Fields	Chronobiology; Neuroethology;
Institutions	Chair of the Department of Neurobiology at UMass Medical School (2001–2013); Higgins Family Professor of Neuroscience UMass Medical School (2001–2017); Distinguished Professor of Neurobiology at UMass Medical School (2014–2017); Distinguished Professor Emeritus of Neurobiology at UMass Medical School (2017–);

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Steven M. Reppert (born September 4, 1946) is an American neuroscientist known for his contributions to the fields of chronobiology and neuroethology. His research has focused primarily on the physiological, cellular, and molecular basis of circadian rhythms in mammals and more recently on the navigational mechanisms of migratory monarch butterflies. He was the Higgins Family Professor of Neuroscience at the University of Massachusetts Medical School from 2001 to 2017, and from 2001 to 2013 was the founding chair of the Department of Neurobiology. Reppert stepped down as chair in 2014. He is currently distinguished professor emeritus of neurobiology.

Biography

Early life

Steven Reppert grew up in the village of Pender, Nebraska, and graduated from Pender Public High School in 1964. His interest in science began in childhood with the cecropia moth—an insect made famous by Harvard biologist Carroll M. Williams, who used the moth in his pioneering work on the role of juvenile hormone in molting and metamorphosis.^[1] Reppert continues to rear cecropia from egg to adult each summer.

Education and career

Reppert received his BS and MD in 1973 (with distinction) from the University of Nebraska College of Medicine and was elected as a medical student to the Alpha Omega Alpha Honor Medical Society. From 1973 to 1976 he did an internship and residency in pediatrics at the Massachusetts General Hospital. From 1976 to 1979 Reppert was a postdoctoral fellow in neuroendocrinology at the National Institute of Child Health and Human Development in Bethesda, Maryland, in David C. Klein's laboratory, which focuses on the pineal gland and circadian biology.^[2] Reppert was on the faculty at the Massachusetts General Hospital and Harvard Medical School beginning in 1979 and was promoted to professor in 1993; he directed the Laboratory of Developmental Chronobiology at the Massachusetts General Hospital from 1983 to 2001, when he moved to the University of Massachusetts Medical School.^[3]

Research

Reppert has published more than 180 papers. He is the principal inventor on seven patents derived from his research.^[4]

Fetal circadian clocks

Rodent studies have shown that the master brain clock in the suprachiasmatic nucleus (SCN) is functional in the fetus before the fetal brain is capable of registering the presence of light. Reppert and colleagues reported that the fetal SCN is entrained to the light-dark cycle before the retinohypothalamic pathway innervates the SCN from the eye.^[5] This finding indicates that the mother, and her entrainment to ambient light-dark cycles, provides the necessary information to the fetus for synchronization. As Reppert states, “Mom is functioning as the transducer for the fetal circadian system. She takes in light information to her circadian system, and then that is communicated to the fetal circadian system.”^[6] This fetal entrainment persists into the postnatal period and ensures that neonatal behavioral patterns are properly tuned with the environment. Dopamine and melatonin can both act as perinatal maternal entraining signals.^[7]

Mammalian circadian clocks

Steven Reppert and colleagues have made seminal contributions that provide insight into the mammalian circadian clock mechanism.

Cell autonomy in the SCN

Reppert and colleagues discovered that the SCN contains a large population of autonomous, single-cell circadian oscillators.^[8] They cultured cells from neonatal rat SCN on fixed microelectrode array that allowed them to monitor individual SCN neuron activity in culture. Circadian rhythms expressed by neurons in the same culture were not synchronized, indicating that they functioned independently of one another.

Functions of mouse clock genes: PERIOD2 and PERIOD3

Reppert and coworkers also discovered the mouse clock genes mPer2 and mPer3 and defined their functions. They found that the mPER2 and mPER3 proteins, as well as the previously discovered mPER1, share several regions of homology with one another and with Drosophila PER.^[9]^[10] Reppert and coworkers found different light responses among the three Per genes.^[10] Unlike mPer1 and mPer2 mRNA levels, mPer3 mRNA levels are not acutely altered by light exposure during the subjective night. They also found that mPer1–3 are widely expressed in tissues outside the brain, including the liver, skeletal muscles, and testis. To determine the function of mPER1–3, Reppert and colleagues disrupted the three genes encoding them.^[11] Using double-mutant mice, they showed that mPER3 functions outside the core circadian clockwork, whereas both mPER1 and mPER2 are necessary for rhythmicity.

Negative transcriptional feedback loop

Reppert and colleagues discovered that the two mouse cryptochromes, mCRY1 and mCRY2, function as the primary transcriptional repressors of clock gene expression, and the mPER proteins are necessary for CRY nuclear translocation.^[12] This work provided the first portrayal of a negative transcriptional feedback loop as the major gear driving the mouse molecular clock.^[13]

Interlocking transcriptional feedback loops

Reppert and colleagues found that the core mechanisms for the SCN in mammals consist of interacting positive and negative transcriptional feedback loops.^[14] The first loop is an autoregulatory negative transcriptional feedback loop in which the mCRY proteins negatively regulate mCry and mPer gene transcription. The second interlocking feedback loop involves the rhythmic regulation of Bmal1. Rhythmicity of Bmal1 is not necessary for clockwork function, but it helps modulate the robustness of rhythmicity.

CLOCK and NPAS2

Reppert and colleagues discovered that the transcription factors CLOCK and NPAS2 have overlapping roles in the SCN, revealing a new and unexpected role for NPAS2.^[15] His lab observed that CLOCK-deficient mice continue to have behavioral and molecular rhythms, which showed that CLOCK is not essential for circadian rhythm in locomotor activity in mice. They then determined, by investigating CLOCK-deficient mice, that NPAS2 is a paralog of CLOCK and can functionally substitute CLOCK by dimerizing with BMAL1. Finally, they found—by investigating CLOCK-deficient, NPAS2-deficient, and double-mutant mice—that circadian rhythms in peripheral oscillators require CLOCK.^[15] Thus, there is a fundamental difference between CLOCK and NPAS2 that is tissue dependent.

Mammalian melatonin receptors

In 1994, Reppert cloned human and sheep Mel_1a melatonin receptor, the first in a family of GPCRs that bind the pineal hormone melatonin, and localized its expression in the mammalian brain to the SCN and the hypophyseal pars tuberalis.^[16] Mel_1a is believed to be responsible for the circadian effects of melatonin and the reproductive actions in seasonal breeding mammals.^[16]

In 1995, Reppert cloned and characterized the Mel_1b melatonin receptor. He and colleagues found that the receptor was predominantly expressed in the retina, where it is believed to modify light-dependent retinal functions.^[17] They identified outbred populations of Siberian hamsters that lacked functional Mel_1b but maintained circadian and reproductive responses to melatonin;^[18] these data indicate that Mel_1b is not necessary for the circadian and reproductive actions of melatonin, which instead depend on Mel_1a.

Elucidation of the molecular nature of the melatonin receptors has facilitated definition of their ligand-binding characteristics and aided the development of melatonin analogs that are now used to treat sleep disorders and depression.^[16]

Insect cryptochromes

In 2003, Reppert began investigating the functional and evolutionary properties of the CRY protein in the monarch butterfly. He identified two Cry genes in the monarch, Cry1 and Cry2.^[19] His work demonstrated that the monarch CRY1 protein is functionally analogous to Drosophila CRY, the blue-light photoreceptor necessary for photoentrainment in the fly. He also demonstrated that monarch CRY2 is functionally analogous to vertebrate CRYs and that monarch CRY2 acts as a potent transcriptional repressor in the circadian clock transcriptional translation feedback loop of the butterfly, as his group previously showed for the two mouse CRYs.^[12] These data propose the existence of a novel circadian clock unique to some non-drosophilid insects that possesses mechanisms characteristic of both the Drosophila and the mammalian clocks.^[20] Other insects, such as bees and ants, possess only a vertebrate-like CRY, and their circadian clocks are even more vertebrate like.^[21] Drosophila is the only known insect that does not possess a vertebrate-like CRY.

In 2008, Reppert and colleagues discovered the necessity of CRY for light-dependent magnetoreception responses in Drosophila. They also showed that magnetoreception requires UVA/blue light, the spectrum corresponding with the action spectrum of Drosophila CRY.^[22] These data were the first to genetically implicate CRY as a component of the input pathway or the chemical-based pathway of magnetoreception. Applying these findings to his work with the monarch, Reppert’s group showed that both monarch CRY1 and CRY2 proteins, when expressed as a transgene in CRY-deficient flies, successfully restore light-dependent magnetosensitivity function. These results propose the presence of a CRY-mediated magnetosensitivity system in monarchs that may act in concordance with the sun compass to aid navigation. In 2011, Reppert's lab also discovered that human CRY2 can substitute as a functional magnetoreceptor in CRY-deficient flies, a discovery that warrants additional research into magnetosensitivity in humans.^[23]^[24] However, interpretation of the above CRY-dependent magnet work needs to be viewed in the context of a paper by Bassetto et al. 2023 that suggests that there is no evidence for magnetic field effects on behaviour in Drosophila.^[25] Moreover, the authors could not reproduce magnetosensitivity in Drosophila using the binary T-maze apparatus developed in Reppert’s lab.^[22] Reppert defends the work from his lab showing fruit fly magnetosensitivity and questions the conclusions reported in Bassetto et al., 2023.^[26] Further work is needed to refute or verify the proposed lack of magnetoreception in Drosophila.

Monarch butterfly migration

Since 2002, Reppert and coworkers have pioneered the study of the biological basis of monarch butterfly migration.^[27]^[28] Each fall, millions of monarchs from the eastern United States and southeastern Canada migrate as much as 4,000 km to overwinter in roosts in Central Mexico.^[29] Monarch migration is not a learned activity, given that migrants flying south are at least two generations removed from the previous year's migrants.^[30] Thus, migrating monarchs must have some genetically based navigational mechanism.

Reppert and colleagues have focused on a novel circadian clock mechanism and its role in time-compensated sun compass orientation, a major navigational strategy that butterflies use during their fall migration.^[29] Using clock-shift experiments, they showed that the circadian clock must interact with the sun compass to enable migrants to maintain a southerly flight direction as the sun moves daily across the sky.^[31] Reppert collaborated with Eli Shlizerman at the University of Washington and Daniel Forger at the University of Michigan to propose a working mathematical model of the time-compensated sun compass.^[32]

Clockwork mechanism

The monarch clockwork model, which has both Drosophila-like and mammal-like aspects, is unique because it employs two distinct CRY proteins. As presented in a review article,^[28] the clock mechanism, on a gene/protein level, operates as follows:

In an autoregulatory transcriptional feedback loop, heterodimers of CLOCK (CLK) and CYCLE (CYC) form and drive the transcription of the Per, Tim, and Cry2 genes.
TIM, PER, and CRY2 proteins are translated and form complexes in the cytoplasm.
24 hours later, CRY2 returns to the nucleus and inhibits CLK:CYC transcription.
Meanwhile, PER is progressively phosphorylated, which may aid CRY2 translocation into the nucleus.
CRY1 protein is a circadian photoreceptor that, when exposed to light, causes TIM degradation, allowing light to gain access to the central clock mechanism for photic entrainment.

Antennal clocks

Reppert’s lab expanded upon Fred Urquhart's postulation that antennae play a role in monarch migration. In 2009 Reppert and coworkers Christine Merlin and Robert Gegear reported that, despite previous assumptions that the time-compensation clocks are located exclusively in the brain, there are also clocks located in the antennae, which "are necessary for proper time-compensated sun compass orientation in migratory monarch butterflies.”^[33] They concluded this by comparing the sun compass orientation of monarch migrants with intact antennae and those whose antennae had been removed.^[33] Reppert's lab also studied antennae in vitro and found that antennal clocks can be directly entrained by light and can function independently from the brain.^[33] Further research is needed, however, on the interaction between the circadian clocks in monarch butterfly's antennae and the sun compass in the brain.

In 2012, Reppert and colleagues determined that only a single antenna is sufficient for sun compass orientation. They did so by painting one antenna black to cause discordant light exposure between the two antennae; the single not-painted antenna was sufficient for orientation. All four clock genes (per, tim, cry1, and cry2) were expressed in the various studied areas of the antenna, suggesting that "light entrained circadian clocks are distributed throughout the length of the monarch butterfly antenna."^[34]

In 2013, Reppert and Patrick Guerra showed that spring remigrants also use an antenna-dependent time-compensated sun compass to direct their northward flight from Mexico to the southern United States.^[35]

Sun compass

Using anatomical and electrophysiological studies of the monarch butterfly brain, Stanley Heinze working in Reppert’s lab provided evidence that the central complex, a midline structure in the central brain, is likely the site of the sun compass.^[36]

Magnetic compass

Reppert and colleagues Patrick Guerra and Robert Gegear showed that migratory monarchs can use a light-dependent, inclination-based, magnetic compass for navigation on overcast days.^[37] Genetic studies from Christine Merlin’s laboratory show that the photoreceptive CRY1 protein is essential for the monarch’s light-sensitive magnetic compass.^[38] The successful use of reverse genetics in monarchs would indicate that the butterfly is an excellent choice for helping to delineate the molecular mechanism underlying light-dependent magnetosensing in the context of compass navigation.

Temperature

Reppert and Patrick Guerra showed that fall migrants prematurely exposed to overwintering-like coldness reverse their flight orientation to the north. The temperature microenvironment at the overwintering site is essential for successful completion of the migration cycle: without cold exposure, aged migrants continue to orient to the south. The discovery that coldness triggers the northward flight direction in spring remigrants underscores how vulnerable the migration may be to climate change.^[39]^[40]

Monarch butterfly genome

In 2011, Reppert and colleagues presented the draft sequence of the monarch butterfly genome and a set 16,866 protein-coding genes. This is the first characterized genome of a butterfly and of a long-distance migratory species.^[41]^[42]^[43]

In 2012, Reppert and colleagues established MonarchBase, an integrated database for the genome of Danaus plexippus. The goal of the project was to make genomic and proteomic information about monarch butterflies accessible to biological and lepidopteran communities.^[44]

In 2013, Christine Merlin and Scot Wolfe developed in Reppert’s lab a novel gene-targeting approach in monarchs that uses a zinc finger nuclease strategy to define the essential nature of CRY2 for clockwork function in lepidopterans.^[45] Targeted mutagenesis of Cry2 indeed resulted in the in vivo disruption of circadian behavior and the molecular clock mechanism. Further work in Merlin’s lab has shown that nuclease strategies are powerful tools for targeting additional clock genes in monarchs and altering gene function.^[46]

In 2016, Reppert collaborated with Marcus Kronforst at the University of Chicago and others to use population genetic studies to define the evolutionary history of the monarch migration.^[47]

Awards and honors

Charles King Trust Research Fellowship, 1981–1984
Basil O'Connor Starter Scholar Research Award, March of Dimes Fund, 1981–1983
Established Investigator Award of the American Heart Association, 1985–1990
Fellow, American Society for Clinical Investigation, elected 1987
E. Mead Johnson Award for Outstanding Research, 1989^[48]
NIH-NICHD MERIT Award, 1992–2002
Honorary master's degree, Harvard University, 1993
Higgins Family Professor of Neuroscience, University of Massachusetts Medical School, 2001–2017
President, Society for Research on Biological Rhythms, 2004
Fellow of the American Association for the Advancement of Science, elected 2011^[49]
Gregor J. Mendel Honorary Medal for Merit in the Biological Sciences from the Academy of Sciences of the Czech Republic, 2012^[50]
Honorary doctorate, University of South Bohemia, Czech Republic, 2013^[51]
Chancellor’s Medal for Distinguished Scholarship, University of Massachusetts Medical School, 2016^[52]

References

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^ Klinkenborg, Verlyn (5 January 1997). "Awakening to Sleep". New York Times.
^ Davis, Fred C.; Reppert, Steven M. (2001). "Development of Mammalian Circadian Rhythms". Handbook of Behavioral Neurobiology. Vol. 12. pp. 247–90. doi:10.1007/978-1-4615-1201-1_10. ISBN 978-0-306-46504-8.
^ Welsh, David K; Logothetis, Diomedes E; Meister, Markus; Reppert, Steven M (1995). "Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms". Neuron. 14 (4): 697–706. doi:10.1016/0896-6273(95)90214-7. PMID 7718233.
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^ Bae, Kiho; Jin, Xiaowei; Maywood, Elizabeth S.; Hastings, Michael H.; Reppert, Steven M.; Weaver, David R. (2001). "Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock". Neuron. 30 (2): 525–36. doi:10.1016/S0896-6273(01)00302-6. PMID 11395012.
^ ^a ^b Kume, Kazuhiko; Zylka, Mark J; Sriram, Sathyanarayanan; Shearman, Lauren P; Weaver, David R; Jin, Xiaowei; Maywood, Elizabeth S; Hastings, Michael H; Reppert, Steven M (1999). "MCRY1 and mCRY2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop". Cell. 98 (2): 193–205. doi:10.1016/S0092-8674(00)81014-4. PMID 10428031.
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^ ^a ^b Debruyne, Jason P; Weaver, David R; Reppert, Steven M (2007). "CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock". Nature Neuroscience. 10 (5): 543–5. doi:10.1038/nn1884. PMC 2782643. PMID 17417633.
^ ^a ^b ^c Reppert, Steven M.; Weaver, David R.; Ebisawa, Takashi (1994). "Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses". Neuron. 13 (5): 1177–85. doi:10.1016/0896-6273(94)90055-8. PMID 7946354. S2CID 19805481.
^ Reppert, S. M.; Godson, C.; Mahle, C. D.; Weaver, D. R.; Slaugenhaupt, S. A.; Gusella, J. F. (1995). "Molecular characterization of a second melatonin receptor expressed in human retina and brain: The Mel1b melatonin receptor". Proceedings of the National Academy of Sciences. 92 (19): 8734–8. Bibcode:1995PNAS...92.8734R. doi:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.
^ Weaver, DR; Liu, C; Reppert, SM (1996). "Nature's knockout: The Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters". Molecular Endocrinology. 10 (11): 1478–87. doi:10.1210/MEND.10.11.8923472. PMID 8923472.
^ Zhu, Haisun; Yuan, Quan; Briscoe, Oren; Froy, Amy; Casselman, Steven M.; Reppert, SM (2005). "The two CRYs of the butterfly". Current Biology. 15 (23): R953–4. Bibcode:2005CBio...15.R953Z. doi:10.1016/j.cub.2005.11.030. PMID 16332522.
^ Zhu, Haisun; Sauman, Ivo; Yuan, Quan; Casselman, Amy; Emery-Le, Myai; Emery, Patrick; Reppert, Steven M. (2008). "Cryptochromes Define a Novel Circadian Clock Mechanism in Monarch Butterflies That May Underlie Sun Compass Navigation". PLOS Biology. 6 (1): e4. doi:10.1371/journal.pbio.0060004. PMC 2174970. PMID 18184036.
^ Yuan, Q.; Metterville, D.; Briscoe, A. D.; Reppert, S. M. (2007). "Insect Cryptochromes: Gene Duplication and Loss Define Diverse Ways to Construct Insect Circadian Clocks". Molecular Biology and Evolution. 24 (4): 948–55. doi:10.1093/molbev/msm011. PMID 17244599.
^ ^a ^b Gegear, Robert J.; Casselman, Amy; Waddell, Scott; Reppert, Steven M. (2008). "Cryptochrome mediates light-dependent magnetosensitivity in Drosophila". Nature. 454 (7207): 1014–8. Bibcode:2008Natur.454.1014G. doi:10.1038/nature07183. PMC 2559964. PMID 18641630.
^ Foley, Lauren E.; Gegear, Robert J.; Reppert, Steven M. (2011). "Human cryptochrome exhibits light-dependent magnetosensitivity". Nature Communications. 2 (6): 356–. Bibcode:2011NatCo...2..356F. doi:10.1038/ncomms1364. PMC 3128388. PMID 21694704.
^ Matt Ridley (February 1, 2013). "Insects that put Google Maps to shame". Wall Street Journal. Retrieved September 28, 2013.
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^ ^a ^b Reppert, Steven M.; Guerra, Patrick A.; Merlin, Christine (2016). "Neurobiology of Monarch Butterfly Migration". Annual Review of Entomology. 61: 25–42. doi:10.1146/annurev-ento-010814-020855. PMID 26473314.
^ ^a ^b Reppert, Steven M.; Gegear, Robert J.; Merlin, Christine (2010). "Navigational mechanisms of migrating monarch butterflies". Trends in Neurosciences. 33 (9): 399–406. doi:10.1016/j.tins.2010.04.004. PMC 2929297. PMID 20627420.
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^ ^a ^b ^c Merlin, C.; Gegear, R. J.; Reppert, S. M. (2009). "Antennal Circadian Clocks Coordinate Sun Compass Orientation in Migratory Monarch Butterflies". Science. 325 (5948): 1700–4. Bibcode:2009Sci...325.1700M. doi:10.1126/science.1176221. PMC 2754321. PMID 19779201.
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^ Heinze, Stanley; Florman, Jeremy; Asokaraj, Surainder; El Jundi, Basil; Reppert, Steven M. (2013). "Anatomical basis of sun compass navigation II: The neuronal composition of the central complex of the monarch butterfly". Journal of Comparative Neurology. 521 (2): 267–98. doi:10.1002/cne.23214. PMID 22886450. S2CID 205682692.
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^ Wan, Guijun; Hayden, Ashley N.; Iams, Samanatha E.; Merlin, Christine (2021). "Cryptochrome 1 mediates light-dependent inclination magnetosensing in monarch butterflies". Nature Communications. 12 (1): 771. Bibcode:2021NatCo..12..771W. doi:10.1038/s41467-021-21002-z. PMC 7859408. PMID 33536422.
^ Nayantara Narayanan; ClimateWire (February 22, 2013). "Climate change may disrupt monarch butterfly migration". Scientific American. Retrieved September 28, 2013.
^ Meghan Rosen (March 23, 2013). "Chill turns monarchs north". ScienceNews. Archived from the original on October 2, 2013. Retrieved September 28, 2013.
^ Zhan, Shuai; Merlin, Christine; Boore, Jeffrey L.; Reppert, Steven M. (2011). "The Monarch Butterfly Genome Yields Insights into Long-Distance Migration". Cell. 147 (5): 1171–85. doi:10.1016/j.cell.2011.09.052. PMC 3225893. PMID 22118469.
^ Stensmyr, Marcus C.; Hansson, Bill S. (2011). "A Genome Befitting a Monarch". Cell. 147 (5): 970–2. doi:10.1016/j.cell.2011.11.009. PMID 22118454.
^ Johnson, Carolyn Y. (23 November 2011). "Monarch butterfly genome sequenced". The Boston Globe. Boston, MA. Retrieved 9 January 2012.
^ Zhan, S.; Reppert, S. M. (2012). "MonarchBase: The monarch butterfly genome database". Nucleic Acids Research. 41 (Database issue): D758–63. doi:10.1093/nar/gks1057. PMC 3531138. PMID 23143105.
^ Merlin, C.; Beaver, L. E.; Taylor, O. R.; Wolfe, S. A.; Reppert, S. M. (2012). "Efficient targeted mutagenesis in the monarch butterfly using zinc-finger nucleases" (PDF). Genome Research. 23 (1): 159–68. doi:10.1101/gr.145599.112. PMC 3530676. PMID 23009861.
^ Markert, Matthew J.; Zhang, Ying; Enuameh, Metewo S.; Reppert, Steven M.; Wolfe, Scot A.; Merlin, Christine (2016). "Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis". G3 (Bethesda). 6 (4): 905–15. doi:10.1534/g3.116.027029. PMC 4825660. PMID 26837953.
^ Zhan, Shuai; Zhang, Wei; Niitepõld, Kristjan; Hsu, Jeremy; Fernández Haeger, Juan; Zalucki, Myron P.; Altizer, Sonia; de Roode, Jacobus C.; Reppert, Steven M.; Kronforst, Marcus R. (2014). "The genetics of monarch butterfly migration and warning colouration". Nature. 514 (7522): 317–21. Bibcode:2014Natur.514..317Z. doi:10.1038/nature13812. PMC 4331202. PMID 25274300.
^ "SPR Member Info". Archived from the original on 2010-08-22. Retrieved 2010-08-30.
^ "AAAS Honorary Fellows".
^ Czech News Agency (ČTK). "Academy of Science awards American researcher Reppert". Prague Daily Monitor.
^ "Neurobiolog Steven M. Reppert převzal čestný doktorát Jihočeské univerzity". University of South Bohemia.
^ Larson, Lisa M. (14 September 2016). "Convocation 2016 recognizes Chancellor's Medal recipients; faculty invested as named chairs". UMassMedNOW. Worcester, MA. Retrieved 16 June 2019.

External links

Reppert Lab website
UMass Medical School faculty page
Search Results for author Reppert SM on PubMed.
Steven M. Reppert publications indexed by Google Scholar
MonarchBase
Steven Reppert Seminar: Neurobiology of Monarch Butterfly Migration

[1] Pappenheimer, A.M. Jr (1995). "Carroll Milton Williams: December 2, 1916–October 11, 1991". NAS Biographical Memoirs. 68: 413–434. PMID 11616356.

[2] "Neuroscience@NIH". NIH. Retrieved April 24, 2013.

[3] "Search | Profiles RNS".

[4] "Steven M Reppert, Inventor, Newton, MA".

[5] Reppert, Steven M. (1985). "Maternal Entrainment of the Developing Orcadian Systema". Annals of the New York Academy of Sciences. 453 (1): 162–9. Bibcode:1985NYASA.453..162R. doi:10.1111/j.1749-6632.1985.tb11808.x. PMID 3865580. S2CID 45891069.

[6] Klinkenborg, Verlyn (5 January 1997). "Awakening to Sleep". New York Times.

[7] Davis, Fred C.; Reppert, Steven M. (2001). "Development of Mammalian Circadian Rhythms". Handbook of Behavioral Neurobiology. Vol. 12. pp. 247–90. doi:10.1007/978-1-4615-1201-1_10. ISBN 978-0-306-46504-8.

[8] Welsh, David K; Logothetis, Diomedes E; Meister, Markus; Reppert, Steven M (1995). "Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms". Neuron. 14 (4): 697–706. doi:10.1016/0896-6273(95)90214-7. PMID 7718233.

[9] Shearman, Lauren P.; Zylka, Mark J.; Weaver, David R.; Kolakowski Jr, Lee F.; Reppert, Steven M. (1997). "Two period Homologs: Circadian Expression and Photic Regulation in the Suprachiasmatic Nuclei". Neuron. 19 (6): 1261–9. doi:10.1016/S0896-6273(00)80417-1. PMID 9427249.

[Zylka-10] Zylka, Mark J; Shearman, Lauren P; Weaver, David R; Reppert, Steven M (1998). "Three period Homologs in Mammals: Differential Light Responses in the Suprachiasmatic Circadian Clock and Oscillating Transcripts Outside of Brain". Neuron. 20 (6): 1103–10. doi:10.1016/S0896-6273(00)80492-4. PMID 9655499.

[11] Bae, Kiho; Jin, Xiaowei; Maywood, Elizabeth S.; Hastings, Michael H.; Reppert, Steven M.; Weaver, David R. (2001). "Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock". Neuron. 30 (2): 525–36. doi:10.1016/S0896-6273(01)00302-6. PMID 11395012.

[Kune-12] Kume, Kazuhiko; Zylka, Mark J; Sriram, Sathyanarayanan; Shearman, Lauren P; Weaver, David R; Jin, Xiaowei; Maywood, Elizabeth S; Hastings, Michael H; Reppert, Steven M (1999). "MCRY1 and mCRY2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop". Cell. 98 (2): 193–205. doi:10.1016/S0092-8674(00)81014-4. PMID 10428031.

[13] Kreeger, Karen Young. "Collecting Clues to the Mammalian Clock". The Scientist.

[14] Shearman, L. P.; Sriram, S; Weaver, DR; Maywood, ES; Chaves, I; Zheng, B; Kume, K; Lee, CC; Van Der Horst, GT; Hastings, MH; Reppert, SM (2000). "Interacting Molecular Loops in the Mammalian Circadian Clock". Science. 288 (5468): 1013–9. Bibcode:2000Sci...288.1013S. doi:10.1126/science.288.5468.1013. PMID 10807566.

[DeBruyne-15] Debruyne, Jason P; Weaver, David R; Reppert, Steven M (2007). "CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock". Nature Neuroscience. 10 (5): 543–5. doi:10.1038/nn1884. PMC 2782643. PMID 17417633.

[Reppert_1994-16] Reppert, Steven M.; Weaver, David R.; Ebisawa, Takashi (1994). "Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses". Neuron. 13 (5): 1177–85. doi:10.1016/0896-6273(94)90055-8. PMID 7946354. S2CID 19805481.

[Reppert_1995-17] Reppert, S. M.; Godson, C.; Mahle, C. D.; Weaver, D. R.; Slaugenhaupt, S. A.; Gusella, J. F. (1995). "Molecular characterization of a second melatonin receptor expressed in human retina and brain: The Mel1b melatonin receptor". Proceedings of the National Academy of Sciences. 92 (19): 8734–8. Bibcode:1995PNAS...92.8734R. doi:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.

[18] Weaver, DR; Liu, C; Reppert, SM (1996). "Nature's knockout: The Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters". Molecular Endocrinology. 10 (11): 1478–87. doi:10.1210/MEND.10.11.8923472. PMID 8923472.

[19] Zhu, Haisun; Yuan, Quan; Briscoe, Oren; Froy, Amy; Casselman, Steven M.; Reppert, SM (2005). "The two CRYs of the butterfly". Current Biology. 15 (23): R953–4. Bibcode:2005CBio...15.R953Z. doi:10.1016/j.cub.2005.11.030. PMID 16332522.

[Reppert_2008-20] Zhu, Haisun; Sauman, Ivo; Yuan, Quan; Casselman, Amy; Emery-Le, Myai; Emery, Patrick; Reppert, Steven M. (2008). "Cryptochromes Define a Novel Circadian Clock Mechanism in Monarch Butterflies That May Underlie Sun Compass Navigation". PLOS Biology. 6 (1): e4. doi:10.1371/journal.pbio.0060004. PMC 2174970. PMID 18184036.

[21] Yuan, Q.; Metterville, D.; Briscoe, A. D.; Reppert, S. M. (2007). "Insect Cryptochromes: Gene Duplication and Loss Define Diverse Ways to Construct Insect Circadian Clocks". Molecular Biology and Evolution. 24 (4): 948–55. doi:10.1093/molbev/msm011. PMID 17244599.

[pmid18641630-22] Gegear, Robert J.; Casselman, Amy; Waddell, Scott; Reppert, Steven M. (2008). "Cryptochrome mediates light-dependent magnetosensitivity in Drosophila". Nature. 454 (7207): 1014–8. Bibcode:2008Natur.454.1014G. doi:10.1038/nature07183. PMC 2559964. PMID 18641630.

[23] Foley, Lauren E.; Gegear, Robert J.; Reppert, Steven M. (2011). "Human cryptochrome exhibits light-dependent magnetosensitivity". Nature Communications. 2 (6): 356–. Bibcode:2011NatCo...2..356F. doi:10.1038/ncomms1364. PMC 3128388. PMID 21694704.

[24] Matt Ridley (February 1, 2013). "Insects that put Google Maps to shame". Wall Street Journal. Retrieved September 28, 2013.

[pmid37558871-25] Bassetto, Marco; Reichl, Thomas; Kobylkov, Dmitry; Kattnig, Daniel R.; Winklhofer, Michael; Hore, P.J.; Mouritsen, Henrik (2023). "No evidence for magnetic field effects on the behaviour of Drosophila". Nature. 620 (7974): 595–599. Bibcode:2023Natur.620..595B. doi:10.1038/s41586-023-06397-7. PMC 10432270. PMID 37558871.

[26] Nick Petric Howe; Shamini Bundell (16 August 2023). "Fruit flies ability to sense magnetic fields thrown into doubt". Nature Podcast. Retrieved 16 October 2023.

[pmid19591650-27] Kyriacou, Charalambos P (2009). "Clocks, cryptochromes and Monarch migrations". Journal of Biology. 8 (6): 55. doi:10.1186/jbiol153. PMC 2737371. PMID 19591650.

[pmid26473314-28] Reppert, Steven M.; Guerra, Patrick A.; Merlin, Christine (2016). "Neurobiology of Monarch Butterfly Migration". Annual Review of Entomology. 61: 25–42. doi:10.1146/annurev-ento-010814-020855. PMID 26473314.

[pmid20627420-29] Reppert, Steven M.; Gegear, Robert J.; Merlin, Christine (2010). "Navigational mechanisms of migrating monarch butterflies". Trends in Neurosciences. 33 (9): 399–406. doi:10.1016/j.tins.2010.04.004. PMC 2929297. PMID 20627420.

[30] Brower, L (1996). "Monarch butterfly orientation: Missing pieces of a magnificent puzzle". The Journal of Experimental Biology. 199 (1): 93–103. doi:10.1242/jeb.199.1.93. PMID 9317405.

[31] Froy, O.; Gotter, AL; Casselman, AL; Reppert, SM (2003). "Illuminating the Circadian Clock in Monarch Butterfly Migration". Science. 300 (5623): 1303–5. Bibcode:2003Sci...300.1303F. doi:10.1126/science.1084874. PMID 12764200. S2CID 12011719.

[32] Shlizerman, E; Phillips-Portillo, J; Forger, DB; Reppert, SM (2016). "Neural Integration Underlying a Time-Compensated Sun Compass in the Migratory Monarch Butterfly". Cell Reports. 15 (4): 683–91. doi:10.1016/j.celrep.2016.03.057. PMC 5063661. PMID 27149852.

[Reppert_2009-33] Merlin, C.; Gegear, R. J.; Reppert, S. M. (2009). "Antennal Circadian Clocks Coordinate Sun Compass Orientation in Migratory Monarch Butterflies". Science. 325 (5948): 1700–4. Bibcode:2009Sci...325.1700M. doi:10.1126/science.1176221. PMC 2754321. PMID 19779201.

[34] Guerra, Patrick A.; Merlin, Christine; Gegear, Robert J.; Reppert, Steven M. (2012). "Discordant timing between antennae disrupts sun compass orientation in migratory monarch butterflies". Nature Communications. 3 (7): 958. Bibcode:2012NatCo...3..958G. doi:10.1038/ncomms1965. PMC 3962218. PMID 22805565.

[35] Guerra, Patrick A.; Reppert, Steven M. (2013). "Coldness Triggers Northward Flight in Remigrant Monarch Butterflies". Current Biology. 23 (5): 419–23. Bibcode:2013CBio...23..419G. doi:10.1016/j.cub.2013.01.052. PMID 23434279.

[36] Heinze, Stanley; Florman, Jeremy; Asokaraj, Surainder; El Jundi, Basil; Reppert, Steven M. (2013). "Anatomical basis of sun compass navigation II: The neuronal composition of the central complex of the monarch butterfly". Journal of Comparative Neurology. 521 (2): 267–98. doi:10.1002/cne.23214. PMID 22886450. S2CID 205682692.

[37] Guerra, Patrick A.; Gegear, Robert J.; Reppert, Steven M. (2014). "A magnetic compass aids monarch butterfly migration". Nature Communications. 5: 4164. Bibcode:2014NatCo...5.4164G. doi:10.1038/ncomms5164. PMC 4090716. PMID 24960099.

[38] Wan, Guijun; Hayden, Ashley N.; Iams, Samanatha E.; Merlin, Christine (2021). "Cryptochrome 1 mediates light-dependent inclination magnetosensing in monarch butterflies". Nature Communications. 12 (1): 771. Bibcode:2021NatCo..12..771W. doi:10.1038/s41467-021-21002-z. PMC 7859408. PMID 33536422.

[39] Nayantara Narayanan; ClimateWire (February 22, 2013). "Climate change may disrupt monarch butterfly migration". Scientific American. Retrieved September 28, 2013.

[40] Meghan Rosen (March 23, 2013). "Chill turns monarchs north". ScienceNews. Archived from the original on October 2, 2013. Retrieved September 28, 2013.

[41] Zhan, Shuai; Merlin, Christine; Boore, Jeffrey L.; Reppert, Steven M. (2011). "The Monarch Butterfly Genome Yields Insights into Long-Distance Migration". Cell. 147 (5): 1171–85. doi:10.1016/j.cell.2011.09.052. PMC 3225893. PMID 22118469.

[42] Stensmyr, Marcus C.; Hansson, Bill S. (2011). "A Genome Befitting a Monarch". Cell. 147 (5): 970–2. doi:10.1016/j.cell.2011.11.009. PMID 22118454.

[43] Johnson, Carolyn Y. (23 November 2011). "Monarch butterfly genome sequenced". The Boston Globe. Boston, MA. Retrieved 9 January 2012.

[44] Zhan, S.; Reppert, S. M. (2012). "MonarchBase: The monarch butterfly genome database". Nucleic Acids Research. 41 (Database issue): D758–63. doi:10.1093/nar/gks1057. PMC 3531138. PMID 23143105.

[45] Merlin, C.; Beaver, L. E.; Taylor, O. R.; Wolfe, S. A.; Reppert, S. M. (2012). "Efficient targeted mutagenesis in the monarch butterfly using zinc-finger nucleases" (PDF). Genome Research. 23 (1): 159–68. doi:10.1101/gr.145599.112. PMC 3530676. PMID 23009861.

[46] Markert, Matthew J.; Zhang, Ying; Enuameh, Metewo S.; Reppert, Steven M.; Wolfe, Scot A.; Merlin, Christine (2016). "Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis". G3 (Bethesda). 6 (4): 905–15. doi:10.1534/g3.116.027029. PMC 4825660. PMID 26837953.

[47] Zhan, Shuai; Zhang, Wei; Niitepõld, Kristjan; Hsu, Jeremy; Fernández Haeger, Juan; Zalucki, Myron P.; Altizer, Sonia; de Roode, Jacobus C.; Reppert, Steven M.; Kronforst, Marcus R. (2014). "The genetics of monarch butterfly migration and warning colouration". Nature. 514 (7522): 317–21. Bibcode:2014Natur.514..317Z. doi:10.1038/nature13812. PMC 4331202. PMID 25274300.

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@@ Line 1: / Line 1: @@
+{{short description|American neuroscientist (born 1946)}}
 {{Infobox scientist
-| name        = Steven M. Reppert
+| name              = Steven M. Reppert
-| image       =
+| image             =
-| caption     =
+| caption           =
-| birth_date  = {{Birth date and age|1946|9|4}}
+| birth_date        = {{Birth date and age|1946|9|4}}
-| birth_place = [[Sioux City]], [[Iowa]]
+| birth_place       = [[Sioux City]], [[Iowa]]
-| death_date  =
+| death_date        =
-| death_place =
+| death_place       =
-| children    =
+| children          =
-| spouse      =
+| spouse            =
+| citizenship       = United States
-| residence   = [[Auburndale, Massachusetts]]
+| ethnicity         =
-| citizenship = United States
+| fields            = {{Plainlist|
-| ethnicity  =
-| fields    = {{Plainlist|
 * [[Chronobiology]]
 * [[Neuroethology]]
 }}
-| workplaces = {{Plainlist|
+| workplaces        = {{Plainlist|
 * Chair of the Department of Neurobiology at [[University of Massachusetts Medical School|UMass Medical School]] (2001–2013)
-* Higgins Family Professor of Neuroscience UMass Medical School (2001–)
+* Higgins Family Professor of Neuroscience UMass Medical School (2001–2017)
-* Distinguished Professor of Neurobiology at UMass Medical School (2014–)
+* Distinguished Professor of Neurobiology at UMass Medical School (2014–2017)
+* Distinguished Professor Emeritus of Neurobiology at UMass Medical School (2017–)}}
-}}
-| alma_mater = {{Plainlist|
+| alma_mater        = {{Plainlist|
 * [[University of Nebraska–Lincoln|University of Nebraska, Lincoln]]
 * [[University of Nebraska Medical Center|University of Nebraska, College of Medicine, Omaha]]
@@ Line 29: / Line 29: @@
 | academic_advisors =
 | notable_students  =
-| known_for = {{Plainlist|
+| known_for         = {{Plainlist|
 * Fetal circadian clock
 * Melatonin receptors
@@ Line 35: / Line 35: @@
 * Monarch butterfly sun compass
 }}
-| awards=
+| awards            =
 }}
-'''Steven M. Reppert''' (born September 4, 1946) is an American [[neuroscientist]] known for his contributions to the fields of [[chronobiology]] and [[neuroethology]]. His research has focused primarily on the physiological, cellular, and molecular basis of [[circadian rhythms]] in mammals and more recently on the navigational mechanisms of migratory [[monarch butterflies]]. He is the Higgins Family Professor of Neuroscience at the [[University of Massachusetts Medical School]], and from 2001 to 2013 was the founding chair of the Department of Neurobiology. Reppert stepped down as chair in 2014 to focus exclusively on his research activities. He now holds the additional title of distinguished professor of neurobiology.
+'''Steven M. Reppert''' (born September 4, 1946) is an American [[neuroscientist]] known for his contributions to the fields of [[chronobiology]] and [[neuroethology]]. His research has focused primarily on the physiological, cellular, and molecular basis of [[circadian rhythms]] in mammals and more recently on the navigational mechanisms of migratory [[monarch butterflies]]. He was the Higgins Family Professor of Neuroscience at the [[University of Massachusetts Medical School]] from 2001 to 2017, and from 2001 to 2013 was the founding chair of the Department of Neurobiology. Reppert stepped down as chair in 2014. He is currently distinguished professor emeritus of neurobiology.
 ==Biography==
 ===Early life===
-Steven Reppert grew up in the village of [[Pender, Nebraska]], and graduated from Pender Public High School in 1964. His interest in science began in childhood with the [[cecropia moth]]—an insect made famous by Harvard biologist [[Carroll Williams|Carroll M. Williams]], who used the moth in his pioneering work on the role of [[juvenile hormone]] in molting and metamorphosis.<ref>{{cite journal|last=Pappenheimer|first=A.M. Jr|title=Carroll Milton Williams: December 2, 1916–October 11, 1991|journal=NAS Biographical Memoirs|year=1995|volume=68|pages=413–434|url=http://www.nap.edu/openbook.php?record_id=4990&page=413}}</ref> Reppert continues to rear cecropia from egg to adult each summer, and over his career has published two papers on the circadian system of the cecropia moth.<ref>{{cite journal |doi=10.1016/0896-6273(94)90054-X |title=Cloning of a structural and functional homolog of the circadian clock gene period from the giant silkmoth antheraea pernyi |year=1994 |last1=Reppert |first1=Steven M. |last2=Tsai |first2=Tony |last3=Roca |first3=Alfred L. |last4=Sauman |first4=Ivo |journal=Neuron |volume=13 |issue=5 |pages=1167–76 |pmid=7946353}}</ref><ref>{{cite journal |doi=10.1016/S0896-6273(00)81012-0 |title=Brain Control of Embryonic Circadian Rhythms in the Silkmoth Antheraea pernyi |year=1998 |last1=Sauman |first1=Ivo |last2=Reppert |first2=Steven M |journal=Neuron |volume=20 |issue=4 |pages=741–8 |pmid=9581765}}</ref>
+Steven Reppert grew up in the village of [[Pender, Nebraska]], and graduated from Pender Public High School in 1964. His interest in science began in childhood with the [[cecropia moth]]—an insect made famous by Harvard biologist [[Carroll Williams|Carroll M. Williams]], who used the moth in his pioneering work on the role of [[juvenile hormone]] in molting and metamorphosis.<ref>{{cite journal|last=Pappenheimer|first=A.M. Jr|title=Carroll Milton Williams: December 2, 1916–October 11, 1991|journal=NAS Biographical Memoirs|year=1995|volume=68|pages=413–434|pmid=11616356|url=http://www.nap.edu/openbook.php?record_id=4990&page=413}}</ref> Reppert continues to rear cecropia from egg to adult each summer.
 ===Education and career===
-Reppert received his BS and MD in 1973 (with distinction) from the [[University of Nebraska Medical Center|University of Nebraska College of Medicine]] and was elected as a medical student to the [[Alpha Omega Alpha Honor Medical Society]].  From 1973 to 1976 he did an internship and residency in pediatrics at the [[Massachusetts General Hospital]]. From 1976 to 1979 Reppert was a postdoctoral fellow in [[neuroendocrinology]] at the [[National Institute of Child Health and Human Development]] in Bethesda, Maryland, in David C. Klein's laboratory, which focuses on the pineal gland and circadian biology.<ref>{{cite web|title=Neuroscience@NIH|url=http://neuroscience.nih.gov/Lab.asp?Org_ID=273|publisher=NIH|accessdate=April 24, 2013}}</ref> Reppert was on the faculty at the Massachusetts General Hospital and [[Harvard Medical School]] beginning in 1979 and was promoted to professor in 1993; he directed the Laboratory of Developmental [[Chronobiology]] at the Massachusetts General Hospital from 1983 to 2001, when he moved to the University of Massachusetts Medical School.<ref>http://www.umassmed.edu/neuroscience/faculty/reppert.cfm{{full citation needed}}</ref>
+Reppert received his BS and MD in 1973 (with distinction) from the [[University of Nebraska Medical Center|University of Nebraska College of Medicine]] and was elected as a medical student to the [[Alpha Omega Alpha Honor Medical Society]].  From 1973 to 1976 he did an internship and residency in pediatrics at the [[Massachusetts General Hospital]]. From 1976 to 1979 Reppert was a postdoctoral fellow in [[neuroendocrinology]] at the [[National Institute of Child Health and Human Development]] in Bethesda, Maryland, in David C. Klein's laboratory, which focuses on the pineal gland and circadian biology.<ref>{{cite web|title=Neuroscience@NIH|url=http://neuroscience.nih.gov/Lab.asp?Org_ID=273|publisher=NIH|accessdate=April 24, 2013}}</ref> Reppert was on the faculty at the Massachusetts General Hospital and [[Harvard Medical School]] beginning in 1979 and was promoted to professor in 1993; he directed the Laboratory of Developmental [[Chronobiology]] at the Massachusetts General Hospital from 1983 to 2001, when he moved to the University of Massachusetts Medical School.<ref>{{Cite web | url=http://www.umassmed.edu/neuroscience/faculty/reppert.cfm |title = Search &#124; Profiles RNS}}</ref>
-===Awards and honors===
-Reppert has been a recipient of a Charles King Trust Research Fellowship, a Basil O'Connor Early Scholar Award from the March of Dimes Foundation, and a five-year Established Investigatorship of the [[American Heart Association]]. From 2002 to 2004, he served as president of the [http://www.srbr.org Society for Research on Biological Rhythms].<ref>http://www.srbr.org/Pages/past_meetings.aspx{{full citation needed}}</ref> Other research honors include the [[E. Mead Johnson Award]] for Outstanding Research;<ref>http://www.aps-spr.org/spr/Awards/EMJ.htm</ref> the NIH-NICHD MERIT Award; the Gregor J. Mendel Honorary Medal for Merit in the Biological Sciences from the Academy of Sciences of the Czech Republic;<ref>{{cite web|last=Czech News Agency (ČTK)|title=Academy of Science awards American researcher Reppert|url=http://praguemonitor.com/2013/03/21/academy-science-awards-american-researcher-reppert|publisher=Prague Daily Monitor}}</ref> and an honorary doctorate from the University of South Bohemia.<ref>{{cite web|title=Neurobiolog Steven M. Reppert převzal čestný doktorát Jihočeské univerzity|url=http://www.jcu.cz/news/neurobiolog-steven-m.-reppert-ziskal-cestny-doktorat-jihoceske-univerzity|publisher=University of South Bohemia}}</ref> He is also fellow of the American Association for the Advancement of Science.<ref>http://www.aaas.org/aboutaaas/fellows/{{full citation needed}}</ref>
 ==Research==
-Reppert has published more than 190 papers with over 21,000 citations and an [[h-index]] of 77.<ref>{{cite web|title=Thomson Reuters Web of Science: Citation Report, Reppert SM|url=http://thomsonreuters.com/products_services/science/science_products/a-z/web_of_science/|publisher=Thomson Reuters|accessdate=May 24, 2013|deadurl=yes|archiveurl=https://web.archive.org/web/20110701061806/http://thomsonreuters.com/products_services/science/science_products/a-z/web_of_science/|archivedate=July 1, 2011|df=}}</ref> He is the principal inventor on seven patents derived from his research.<ref>http://www.patentbuddy.com/Inventor/Reppert-Steven-M/1437735{{full citation needed}}</ref>
+Reppert has published more than 180 papers. He is the principal inventor on seven patents derived from his research.<ref>{{Cite web | url=http://www.patentbuddy.com/Inventor/Reppert-Steven-M/1437735 |title = Steven M Reppert, Inventor, Newton, MA}}</ref>
 ===Fetal circadian clocks===
-[[Animal testing on rodents|Rodent studies]] have shown that the master brain clock in the [[suprachiasmatic nucleus]] (SCN) is functional in the fetus before the fetal brain is capable of registering the presence of light. Reppert and colleagues reported that the fetal SCN is entrained to the light-dark cycle before the retinohypothalamic pathway innervates the SCN from the eye.<ref>{{cite journal |doi=10.1111/j.1749-6632.1985.tb11808.x |title=Maternal Entrainment of the Developing Orcadian Systema |year=1985 |last1=Reppert |first1=Steven M. |journal=Annals of the New York Academy of Sciences |volume=453 |pages=162–9 |pmid=3865580}}</ref>  This finding indicates that the mother, and her entrainment to ambient light-dark cycles, provides the necessary information to the fetus for synchronization. As Reppert states, “Mom is functioning as the transducer for the fetal circadian system. She takes in light information to her circadian system, and then that is communicated to the fetal circadian system.”<ref>{{cite web|last=Klinkenborg|first=Verlyn|title=Awakening to Sleep|url=https://www.nytimes.com/1997/01/05/magazine/awakening-to-sleep.html?pagewanted=all&src=pm|publisher=New York Times}}</ref> This fetal entrainment persists into the postnatal period and ensures that neonatal behavioral patterns are properly tuned with the environment. Dopamine and melatonin can both act as perinatal maternal entraining signals.<ref>{{cite book |doi=10.1007/978-1-4615-1201-1_10 |chapter=Development of Mammalian Circadian Rhythms |title=Handbook of Behavioral Neurobiology |series=Handbook of Behavioral Neurobiology |year=2001 |last1=Davis |first1=Fred C. |last2=Reppert |first2=Steven M. |isbn=978-0-306-46504-8 |volume=12 |pages=247–90}}</ref>
+[[Animal testing on rodents|Rodent studies]] have shown that the master brain clock in the [[suprachiasmatic nucleus]] (SCN) is functional in the fetus before the fetal brain is capable of registering the presence of light. Reppert and colleagues reported that the fetal SCN is entrained to the light-dark cycle before the retinohypothalamic pathway innervates the SCN from the eye.<ref>{{cite journal |doi=10.1111/j.1749-6632.1985.tb11808.x |title=Maternal Entrainment of the Developing Orcadian Systema |year=1985 |last1=Reppert |first1=Steven M. |journal=Annals of the New York Academy of Sciences |volume=453 |issue=1 |pages=162–9 |pmid=3865580|bibcode=1985NYASA.453..162R |s2cid=45891069 }}</ref>  This finding indicates that the mother, and her entrainment to ambient light-dark cycles, provides the necessary information to the fetus for synchronization. As Reppert states, “Mom is functioning as the transducer for the fetal circadian system. She takes in light information to her circadian system, and then that is communicated to the fetal circadian system.”<ref>{{cite news|last=Klinkenborg|first=Verlyn|title=Awakening to Sleep|url=https://www.nytimes.com/1997/01/05/magazine/awakening-to-sleep.html?pagewanted=all&src=pm|newspaper=New York Times|date=5 January 1997}}</ref> This fetal entrainment persists into the postnatal period and ensures that neonatal behavioral patterns are properly tuned with the environment. Dopamine and melatonin can both act as perinatal maternal entraining signals.<ref>{{cite book |doi=10.1007/978-1-4615-1201-1_10 |chapter=Development of Mammalian Circadian Rhythms |title=Handbook of Behavioral Neurobiology |year=2001 |last1=Davis |first1=Fred C. |last2=Reppert |first2=Steven M. |isbn=978-0-306-46504-8 |volume=12 |pages=[https://archive.org/details/sensoryintegrati0000unse/page/247 247–90] |chapter-url=https://archive.org/details/sensoryintegrati0000unse/page/247 }}</ref>
 ===Mammalian circadian clocks===
@@ Line 61: / Line 58: @@
 ====Cell autonomy in the SCN====
-Reppert and colleagues discovered that the [[Suprachiasmatic nucleus|SCN]] contains a large population of autonomous, single-cell circadian oscillators.<ref>{{cite journal |doi=10.1016/0896-6273(95)90214-7 |title=Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms |year=1995 |last1=Welsh |first1=David K |last2=Logothetis |first2=Diomedes E |last3=Meister |first3=Markus |last4=Reppert |first4=Steven M |journal=Neuron |volume=14 |issue=4 |pages=697–706 |pmid=7718233}}</ref> They cultured cells from neonatal rat SCN on fixed [[microelectrode array]] that allowed them to monitor individual SCN [[neuron]] activity in culture. Circadian rhythms expressed by neurons in the same culture were not synchronized, indicating that they functioned independently of one another.
+Reppert and colleagues discovered that the [[Suprachiasmatic nucleus|SCN]] contains a large population of autonomous, single-cell circadian oscillators.<ref>{{cite journal |doi=10.1016/0896-6273(95)90214-7 |title=Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms |year=1995 |last1=Welsh |first1=David K |last2=Logothetis |first2=Diomedes E |last3=Meister |first3=Markus |last4=Reppert |first4=Steven M |journal=Neuron |volume=14 |issue=4 |pages=697–706 |pmid=7718233|doi-access=free }}</ref> They cultured cells from neonatal rat SCN on fixed [[microelectrode array]] that allowed them to monitor individual SCN [[neuron]] activity in culture. Circadian rhythms expressed by neurons in the same culture were not synchronized, indicating that they functioned independently of one another.
 ====Functions of mouse clock genes: PERIOD2 and PERIOD3====
-Reppert and coworkers also discovered the mouse clock genes ''mPer2'' and ''mPer3'' and defined their functions. They found that the [[PER2|mPER2]] and [[PER3|mPER3]] proteins, as well as the previously discovered [[PER1|mPER1]], share several regions of homology with one another and with Drosophila PER.<ref>{{cite journal |doi=10.1016/S0896-6273(00)80417-1 |title=Two period Homologs: Circadian Expression and Photic Regulation in the Suprachiasmatic Nuclei |year=1997 |last1=Shearman |first1=Lauren P. |last2=Zylka |first2=Mark J. |last3=Weaver |first3=David R. |last4=Kolakowski Jr |first4=Lee F. |last5=Reppert |first5=Steven M. |journal=Neuron |volume=19 |issue=6 |pages=1261–9 |pmid=9427249}}</ref><ref name=Zylka>{{cite journal |doi=10.1016/S0896-6273(00)80492-4 |title=Three period Homologs in Mammals: Differential Light Responses in the Suprachiasmatic Circadian Clock and Oscillating Transcripts Outside of Brain |year=1998 |last1=Zylka |first1=Mark J |last2=Shearman |first2=Lauren P |last3=Weaver |first3=David R |last4=Reppert |first4=Steven M |journal=Neuron |volume=20 |issue=6 |pages=1103–10 |pmid=9655499}}</ref>  Reppert and coworkers found different light responses among the three ''Per'' genes.<ref name="Zylka"/>  Unlike ''mPer1'' and ''mPer2'' mRNA levels, ''mPer3'' mRNA levels are not acutely altered by light exposure during the subjective night.  They also found that ''mPer1–3'' are widely expressed in tissues outside the brain, including the liver, skeletal muscles, and testis.  To determine the function of mPER1–3, Reppert and colleagues disrupted the three genes encoding them.<ref>{{cite journal |doi=10.1016/S0896-6273(01)00302-6 |title=Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock |year=2001 |last1=Bae |first1=Kiho |last2=Jin |first2=Xiaowei |last3=Maywood |first3=Elizabeth S. |last4=Hastings |first4=Michael H. |last5=Reppert |first5=Steven M. |last6=Weaver |first6=David R. |journal=Neuron |volume=30 |issue=2 |pages=525–36 |pmid=11395012}}</ref> Using double-mutant mice, they showed that mPER3 functions outside the core circadian clockwork, whereas both mPER1 and mPER2 are necessary for rhythmicity.
+Reppert and coworkers also discovered the mouse clock genes ''mPer2'' and ''mPer3'' and defined their functions. They found that the [[PER2|mPER2]] and [[PER3|mPER3]] proteins, as well as the previously discovered [[PER1|mPER1]], share several regions of homology with one another and with Drosophila PER.<ref>{{cite journal |doi=10.1016/S0896-6273(00)80417-1 |title=Two period Homologs: Circadian Expression and Photic Regulation in the Suprachiasmatic Nuclei |year=1997 |last1=Shearman |first1=Lauren P. |last2=Zylka |first2=Mark J. |last3=Weaver |first3=David R. |last4=Kolakowski Jr |first4=Lee F. |last5=Reppert |first5=Steven M. |journal=Neuron |volume=19 |issue=6 |pages=1261–9 |pmid=9427249|doi-access=free }}</ref><ref name=Zylka>{{cite journal |doi=10.1016/S0896-6273(00)80492-4 |title=Three period Homologs in Mammals: Differential Light Responses in the Suprachiasmatic Circadian Clock and Oscillating Transcripts Outside of Brain |year=1998 |last1=Zylka |first1=Mark J |last2=Shearman |first2=Lauren P |last3=Weaver |first3=David R |last4=Reppert |first4=Steven M |journal=Neuron |volume=20 |issue=6 |pages=1103–10 |pmid=9655499|doi-access=free }}</ref> Reppert and coworkers found different light responses among the three ''Per'' genes.<ref name="Zylka"/>  Unlike ''mPer1'' and ''mPer2'' mRNA levels, ''mPer3'' mRNA levels are not acutely altered by light exposure during the subjective night.  They also found that ''mPer1–3'' are widely expressed in tissues outside the brain, including the liver, skeletal muscles, and testis.  To determine the function of mPER1–3, Reppert and colleagues disrupted the three genes encoding them.<ref>{{cite journal |doi=10.1016/S0896-6273(01)00302-6 |title=Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock |year=2001 |last1=Bae |first1=Kiho |last2=Jin |first2=Xiaowei |last3=Maywood |first3=Elizabeth S. |last4=Hastings |first4=Michael H. |last5=Reppert |first5=Steven M. |last6=Weaver |first6=David R. |journal=Neuron |volume=30 |issue=2 |pages=525–36 |pmid=11395012|doi-access=free }}</ref> Using double-mutant mice, they showed that mPER3 functions outside the core circadian clockwork, whereas both mPER1 and mPER2 are necessary for rhythmicity.
 ====Negative transcriptional feedback loop====
-Reppert and colleagues discovered that the two mouse [[cryptochrome]]s, mCRY1 and mCRY2, function as the primary transcriptional repressors of clock gene expression, and the mPER proteins are necessary for CRY nuclear translocation.<ref name=Kune>{{cite journal |doi=10.1016/S0092-8674(00)81014-4 |title=MCRY1 and mCRY2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop |year=1999 |last1=Kume |first1=Kazuhiko |last2=Zylka |first2=Mark J |last3=Sriram |first3=Sathyanarayanan |last4=Shearman |first4=Lauren P |last5=Weaver |first5=David R |last6=Jin |first6=Xiaowei |last7=Maywood |first7=Elizabeth S |last8=Hastings |first8=Michael H |last9=Reppert |first9=Steven M |journal=Cell |volume=98 |issue=2 |pages=193–205 |pmid=10428031 }}</ref> This work provided the first portrayal of a negative transcriptional feedback loop as the major gear driving the mouse molecular clock.<ref>{{cite web|last=Kreeger|first=Karen Young|title=Collecting Clues to the Mammalian Clock|url=http://www.the-scientist.com/?articles.view/articleNo/13970/title/Collecting-Clues-to-the-Mammalian-Clock/|publisher=The Scientist}}</ref>
+Reppert and colleagues discovered that the two mouse [[cryptochrome]]s, mCRY1 and mCRY2, function as the primary transcriptional repressors of clock gene expression, and the mPER proteins are necessary for CRY nuclear translocation.<ref name=Kune>{{cite journal |doi=10.1016/S0092-8674(00)81014-4 |title=MCRY1 and mCRY2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop |year=1999 |last1=Kume |first1=Kazuhiko |last2=Zylka |first2=Mark J |last3=Sriram |first3=Sathyanarayanan |last4=Shearman |first4=Lauren P |last5=Weaver |first5=David R |last6=Jin |first6=Xiaowei |last7=Maywood |first7=Elizabeth S |last8=Hastings |first8=Michael H |last9=Reppert |first9=Steven M |journal=Cell |volume=98 |issue=2 |pages=193–205 |pmid=10428031 |doi-access=free }}</ref> This work provided the first portrayal of a negative transcriptional feedback loop as the major gear driving the mouse molecular clock.<ref>{{cite web|last=Kreeger|first=Karen Young|title=Collecting Clues to the Mammalian Clock|url=http://www.the-scientist.com/?articles.view/articleNo/13970/title/Collecting-Clues-to-the-Mammalian-Clock/|publisher=The Scientist}}</ref>
 ====Interlocking transcriptional feedback loops====
-Reppert and colleagues found that the core mechanisms for the SCN in mammals consist of interacting positive and negative [[Transcription (genetics)|transcriptional]] feedback loops.<ref>{{cite journal |doi=10.1126/science.288.5468.1013 |title=Interacting Molecular Loops in the Mammalian Circadian Clock |year=2000 |last1=Shearman |first1=L. P. |journal=Science |volume=288 |issue=5468 |pages=1013–9 |pmid=10807566 |last2=Sriram |first2=S |last3=Weaver |first3=DR |last4=Maywood |first4=ES |last5=Chaves |first5=I |last6=Zheng |first6=B |last7=Kume |first7=K |last8=Lee |first8=CC |last9=Van Der Horst |first9=GT |last10=Hastings |first10=MH |last11=Reppert |first11=SM }}</ref> The first loop is an autoregulatory negative transcriptional feedback loop in which the mCRY proteins negatively regulate ''mCry'' and ''mPer'' gene transcription. The second interlocking feedback loop involves the rhythmic regulation of ''Bmal1''. Rhythmicity of ''Bmal1'' is not necessary for clockwork function, but it helps modulate the robustness of rhythmicity.
+Reppert and colleagues found that the core mechanisms for the SCN in mammals consist of interacting positive and negative [[Transcription (genetics)|transcriptional]] feedback loops.<ref>{{cite journal |doi=10.1126/science.288.5468.1013 |title=Interacting Molecular Loops in the Mammalian Circadian Clock |year=2000 |last1=Shearman |first1=L. P. |journal=Science |volume=288 |issue=5468 |pages=1013–9 |pmid=10807566 |last2=Sriram |first2=S |last3=Weaver |first3=DR |last4=Maywood |first4=ES |last5=Chaves |first5=I |last6=Zheng |first6=B |last7=Kume |first7=K |last8=Lee |first8=CC |last9=Van Der Horst |first9=GT |last10=Hastings |first10=MH |last11=Reppert |first11=SM |bibcode=2000Sci...288.1013S }}</ref> The first loop is an autoregulatory negative transcriptional feedback loop in which the mCRY proteins negatively regulate ''mCry'' and ''mPer'' gene transcription. The second interlocking feedback loop involves the rhythmic regulation of ''Bmal1''. Rhythmicity of ''Bmal1'' is not necessary for clockwork function, but it helps modulate the robustness of rhythmicity.
 ====CLOCK and NPAS2====
 Reppert and colleagues discovered that the transcription factors CLOCK and [[NPAS2]] have overlapping roles in the SCN, revealing a new and unexpected role for NPAS2.<ref name=DeBruyne>{{cite journal |doi=10.1038/nn1884 |title=CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock |year=2007 |last1=Debruyne |first1=Jason P |last2=Weaver |first2=David R |last3=Reppert |first3=Steven M |journal=Nature Neuroscience |volume=10 |issue=5 |pages=543–5 |pmid=17417633 |pmc=2782643}}</ref> His lab observed that CLOCK-deficient mice continue to have behavioral and molecular rhythms, which showed that CLOCK is not essential for circadian rhythm in locomotor activity in mice.  They then determined, by investigating CLOCK-deficient mice, that NPAS2 is a [[paralog]] of CLOCK and can functionally substitute CLOCK by dimerizing with BMAL1.  Finally, they found—by investigating CLOCK-deficient, NPAS2-deficient, and double-mutant mice—that circadian rhythms in peripheral oscillators require CLOCK.<ref name="DeBruyne"/>  Thus, there is a fundamental difference between CLOCK and NPAS2 that is tissue dependent.
-=== Mammalian melatonin receptors===
+===Mammalian melatonin receptors===
-In 1994, Reppert [[Cloning|cloned]] human and sheep [[Melatonin receptor 1A|Mel<sub>1a</sub>]] [[melatonin receptor]], the first in a family of [[G protein-coupled receptor|GPCR]]s that bind the pineal hormone [[melatonin]], and localized its expression in the mammalian brain to the [[suprachiasmatic nucleus|SCN]] and the [[Pars tuberalis|hypophyseal pars tuberalis]].<ref name=Reppert_1994>{{cite journal |doi=10.1016/0896-6273(94)90055-8 |title=Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses |year=1994 |last1=Reppert |first1=Steven M. |last2=Weaver |first2=David R. |last3=Ebisawa |first3=Takashi |journal=Neuron |volume=13 |issue=5 |pages=1177–85 |pmid=7946354}}</ref> Mel<sub>1a</sub> is believed to be responsible for the circadian effects of melatonin and the reproductive actions in seasonal breeding mammals.<ref name="Reppert_1994" />
+In 1994, Reppert [[Cloning|cloned]] human and sheep [[Melatonin receptor 1A|Mel<sub>1a</sub>]] [[melatonin receptor]], the first in a family of [[G protein-coupled receptor|GPCR]]s that bind the pineal hormone [[melatonin]], and localized its expression in the mammalian brain to the [[suprachiasmatic nucleus|SCN]] and the [[Pars tuberalis|hypophyseal pars tuberalis]].<ref name=Reppert_1994>{{cite journal |doi=10.1016/0896-6273(94)90055-8 |title=Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses |year=1994 |last1=Reppert |first1=Steven M. |last2=Weaver |first2=David R. |last3=Ebisawa |first3=Takashi |journal=Neuron |volume=13 |issue=5 |pages=1177–85 |pmid=7946354|s2cid=19805481 }}</ref> Mel<sub>1a</sub> is believed to be responsible for the circadian effects of melatonin and the reproductive actions in seasonal breeding mammals.<ref name="Reppert_1994" />
-In 1995, Reppert cloned and characterized the [[Melatonin receptor 1B|Mel<sub>1b</sub>]] melatonin receptor. He and colleagues found that the receptor was predominantly expressed in the [[retina]], where it is believed to modify light-dependent retinal functions.<ref name=Reppert_1995>{{cite journal |doi=10.1073/pnas.92.19.8734 |title=Molecular characterization of a second melatonin receptor expressed in human retina and brain: The Mel1b melatonin receptor |year=1995 |last1=Reppert |first1=S. M. |last2=Godson |first2=C. |last3=Mahle |first3=C. D. |last4=Weaver |first4=D. R. |last5=Slaugenhaupt |first5=S. A. |last6=Gusella |first6=J. F. |journal=Proceedings of the National Academy of Sciences |volume=92 |issue=19 |pages=8734–8 |pmid=7568007 |pmc=41041}}</ref> They identified outbred populations of [[Djungarian hamster|Siberian hamsters]] that lacked functional Mel<sub>1b</sub> but maintained circadian and reproductive responses to melatonin;<ref>{{cite journal |pmid=8923472 |year=1996 |last1=Weaver |first1=DR |last2=Liu |first2=C |last3=Reppert |first3=SM |title=Nature's knockout: The Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters |volume=10 |issue=11 |pages=1478–87 |journal=Molecular Endocrinology |doi=10.1210/MEND.10.11.8923472}}</ref> these data indicate that Mel<sub>1b</sub> is not necessary for the circadian and reproductive actions of melatonin, which instead depend on Mel<sub>1a</sub>.
+In 1995, Reppert cloned and characterized the [[Melatonin receptor 1B|Mel<sub>1b</sub>]] melatonin receptor. He and colleagues found that the receptor was predominantly expressed in the [[retina]], where it is believed to modify light-dependent retinal functions.<ref name=Reppert_1995>{{cite journal |doi=10.1073/pnas.92.19.8734 |title=Molecular characterization of a second melatonin receptor expressed in human retina and brain: The Mel1b melatonin receptor |year=1995 |last1=Reppert |first1=S. M. |last2=Godson |first2=C. |last3=Mahle |first3=C. D. |last4=Weaver |first4=D. R. |last5=Slaugenhaupt |first5=S. A. |last6=Gusella |first6=J. F. |journal=Proceedings of the National Academy of Sciences |volume=92 |issue=19 |pages=8734–8 |pmid=7568007 |pmc=41041|bibcode=1995PNAS...92.8734R |doi-access=free }}</ref> They identified outbred populations of [[Djungarian hamster|Siberian hamsters]] that lacked functional Mel<sub>1b</sub> but maintained circadian and reproductive responses to melatonin;<ref>{{cite journal |pmid=8923472 |year=1996 |last1=Weaver |first1=DR |last2=Liu |first2=C |last3=Reppert |first3=SM |title=Nature's knockout: The Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters |volume=10 |issue=11 |pages=1478–87 |journal=Molecular Endocrinology |doi=10.1210/MEND.10.11.8923472|doi-access=free }}</ref> these data indicate that Mel<sub>1b</sub> is not necessary for the circadian and reproductive actions of melatonin, which instead depend on Mel<sub>1a</sub>.
 Elucidation of the molecular nature of the melatonin receptors has facilitated definition of their ligand-binding characteristics and aided the development of melatonin analogs that are now used to treat sleep disorders and depression.<ref name="Reppert_1994" />
 ===Insect cryptochromes===
-In 2003, Reppert began investigating the functional and evolutionary properties of the CRY protein in the monarch butterfly. He identified two ''Cry'' genes in the monarch, ''Cry1'' and ''Cry2''.<ref>{{cite journal |doi=10.1016/j.cub.2005.11.030 |title=The two CRYs of the butterfly |year=2005 |last1=Zhu |first1=Haisun |last2=Yuan |first2=Quan |last3=Briscoe |first3=Oren |last4=Froy |first4=Amy |last5=Casselman |first5=Steven M. |journal=Current Biology |volume=15 |issue=23 |pages=R953–4 |pmid=16332522 |last6=Reppert |first6=SM}}</ref>
+In 2003, Reppert began investigating the functional and evolutionary properties of the CRY protein in the monarch butterfly. He identified two ''Cry'' genes in the monarch, ''Cry1'' and ''Cry2''.<ref>{{cite journal |doi=10.1016/j.cub.2005.11.030 |title=The two CRYs of the butterfly |year=2005 |last1=Zhu |first1=Haisun |last2=Yuan |first2=Quan |last3=Briscoe |first3=Oren |last4=Froy |first4=Amy |last5=Casselman |first5=Steven M. |journal=Current Biology |volume=15 |issue=23 |pages=R953–4 |pmid=16332522 |last6=Reppert |first6=SM|doi-access=free |bibcode=2005CBio...15.R953Z }}</ref>
-His work demonstrated that the monarch CRY1 protein is functionally analogous to ''Drosophila'' CRY, the blue-light photoreceptor necessary for [[Entrainment (chronobiology)|photoentrainment]] in the fly. He also demonstrated that monarch CRY2 is functionally analogous to vertebrate CRYs and that monarch CRY2 acts as a potent transcriptional [[repressor]] in the [[Circadian clock#Transcriptional and translational control|circadian clock transcriptional translation feedback loop]] of the butterfly, as his group previously showed for the two mouse CRYs.<ref name="Kune"/> These data propose the existence of a novel [[circadian clock]] unique to some non-drosophilid insects that possesses mechanisms characteristic of both the ''Drosophila'' and the mammalian clocks.<ref name=Reppert_2008>{{cite journal |doi=10.1371/journal.pbio.0060004 |title=Cryptochromes Define a Novel Circadian Clock Mechanism in Monarch Butterflies That May Underlie Sun Compass Navigation |year=2008 |last1=Zhu |first1=Haisun |last2=Sauman |first2=Ivo |last3=Yuan |first3=Quan |last4=Casselman |first4=Amy |last5=Emery-Le |first5=Myai |last6=Emery |first6=Patrick |last7=Reppert |first7=Steven M. |journal=PLoS Biology |volume=6 |pages=e4 |pmid=18184036 |pmc=2174970}}</ref> Other insects, such as bees and ants, possess only a vertebrate-like CRY, and their circadian clocks are even more vertebrate like.<ref>{{cite journal |doi=10.1093/molbev/msm011 |title=Insect Cryptochromes: Gene Duplication and Loss Define Diverse Ways to Construct Insect Circadian Clocks |year=2007 |last1=Yuan |first1=Q. |last2=Metterville |first2=D. |last3=Briscoe |first3=A. D. |last4=Reppert |first4=S. M. |journal=Molecular Biology and Evolution |volume=24 |issue=4 |pages=948–55 |pmid=17244599}}</ref> ''Drosophila'' is the only known insect that does not possess a vertebrate-like CRY.
+His work demonstrated that the monarch CRY1 protein is functionally analogous to ''Drosophila'' CRY, the blue-light photoreceptor necessary for [[Entrainment (chronobiology)|photoentrainment]] in the fly. He also demonstrated that monarch CRY2 is functionally analogous to vertebrate CRYs and that monarch CRY2 acts as a potent transcriptional [[repressor]] in the [[Circadian clock#Transcriptional and non-transcriptional control|circadian clock transcriptional translation feedback loop]] of the butterfly, as his group previously showed for the two mouse CRYs.<ref name="Kune"/> These data propose the existence of a novel [[circadian clock]] unique to some non-drosophilid insects that possesses mechanisms characteristic of both the ''Drosophila'' and the mammalian clocks.<ref name=Reppert_2008>{{cite journal |doi=10.1371/journal.pbio.0060004 |title=Cryptochromes Define a Novel Circadian Clock Mechanism in Monarch Butterflies That May Underlie Sun Compass Navigation |year=2008 |last1=Zhu |first1=Haisun |last2=Sauman |first2=Ivo |last3=Yuan |first3=Quan |last4=Casselman |first4=Amy |last5=Emery-Le |first5=Myai |last6=Emery |first6=Patrick |last7=Reppert |first7=Steven M. |journal=PLOS Biology |volume=6 |issue=1 |pages=e4 |pmid=18184036 |pmc=2174970 |doi-access=free }}</ref> Other insects, such as bees and ants, possess only a vertebrate-like CRY, and their circadian clocks are even more vertebrate like.<ref>{{cite journal |doi=10.1093/molbev/msm011 |title=Insect Cryptochromes: Gene Duplication and Loss Define Diverse Ways to Construct Insect Circadian Clocks |year=2007 |last1=Yuan |first1=Q. |last2=Metterville |first2=D. |last3=Briscoe |first3=A. D. |last4=Reppert |first4=S. M. |journal=Molecular Biology and Evolution |volume=24 |issue=4 |pages=948–55 |pmid=17244599|doi-access=free }}</ref> ''Drosophila'' is the only known insect that does not possess a vertebrate-like CRY.
+In 2008, Reppert and colleagues discovered the necessity of CRY for light-dependent [[magnetoreception]] responses in ''Drosophila''. They also showed that magnetoreception requires UVA/blue light, the spectrum corresponding with the [[action spectrum]] of ''Drosophila'' CRY.<ref name="pmid18641630">{{cite journal |doi=10.1038/nature07183 |title=Cryptochrome mediates light-dependent magnetosensitivity in Drosophila |year=2008 |last1=Gegear |first1=Robert J. |last2=Casselman |first2=Amy |last3=Waddell |first3=Scott |last4=Reppert |first4=Steven M. |journal=Nature |volume=454 |issue=7207 |pages=1014–8 |pmid=18641630 |pmc=2559964|bibcode=2008Natur.454.1014G }}</ref> These data were the first to genetically implicate CRY as a component of the input pathway or the chemical-based pathway of magnetoreception. Applying these findings to his work with the monarch, Reppert’s group showed that both monarch CRY1 and CRY2 proteins, when expressed as a transgene in CRY-deficient flies, successfully restore light-dependent magnetosensitivity function. These results propose the presence of a CRY-mediated magnetosensitivity system in monarchs that may act in concordance with the sun compass to aid navigation. In 2011, Reppert's lab also discovered that human CRY2 can substitute as a functional magnetoreceptor in CRY-deficient flies, a discovery that warrants additional research into magnetosensitivity in humans.<ref>{{cite journal |doi=10.1038/ncomms1364 |title=Human cryptochrome exhibits light-dependent magnetosensitivity |year=2011 |last1=Foley |first1=Lauren E. |last2=Gegear |first2=Robert J. |last3=Reppert |first3=Steven M. |journal=Nature Communications |volume=2 |pages=356– |pmid=21694704 |pmc=3128388 |issue=6|bibcode=2011NatCo...2..356F }}</ref><ref>{{cite news |title=Insects that put Google Maps to shame |author=Matt Ridley |url=https://www.wsj.com/articles/SB10001424127887323375204578269963079963082 |newspaper=Wall Street Journal |date=February 1, 2013 |accessdate=September 28, 2013 }}</ref> However, interpretation of the above CRY-dependent magnet work needs to be viewed in the context of a paper by Bassetto ''et al.'' 2023  that suggests that there is no evidence for magnetic field effects on behaviour in ''Drosophila''.<ref name = "pmid37558871"> {{cite journal |doi=10.1038/s41586-023-06397-7 |title=No evidence for magnetic field effects on the behaviour of Drosophila. |year=2023 |last1=Bassetto |first1=Marco |last2=Reichl |first2=Thomas |last3=Kobylkov |first3=Dmitry| last4=Kattnig |first4=Daniel R.| last5=Winklhofer|first5 = Michael|last6 = Hore|first6= P.J. | last7=Mouritsen|first7=Henrik |journal=Nature |volume=620 |issue=7974 |pages=595–599|pmid=37558871|pmc=10432270 |doi-access=free |bibcode=2023Natur.620..595B }}</ref> Moreover, the authors could not reproduce magnetosensitivity in ''Drosophila'' using the binary T-maze apparatus developed in Reppert’s lab.<ref name="pmid18641630"/> Reppert defends the work from his lab showing fruit fly magnetosensitivity and questions the conclusions reported in Bassetto ''et al.'', 2023.<ref>{{cite news |title= Fruit flies ability to sense magnetic fields thrown into doubt |author=Nick Petric Howe|author2=Shamini Bundell |url= https://www.nature.com/articles/d41586-023-02590-w|newspaper=Nature Podcast |date= 16 August 2023 |accessdate=16 October 2023}}</ref> Further work is needed to refute or verify the proposed lack of magnetoreception in ''Drosophila''.
-In 2008, Reppert discovered the necessity of ''Cry'' for light-dependent [[magnetoreception]] responses in ''Drosophila''. He also showed that magnetoreception requires UVA/blue light, the spectrum corresponding with the [[action spectrum]] of ''Drosophila'' CRY.<ref>{{cite journal |doi=10.1038/nature07183 |title=Cryptochrome mediates light-dependent magnetosensitivity in Drosophila |year=2008 |last1=Gegear |first1=Robert J. |last2=Casselman |first2=Amy |last3=Waddell |first3=Scott |last4=Reppert |first4=Steven M. |journal=Nature |volume=454 |issue=7207 |pages=1014–8 |pmid=18641630 |pmc=2559964}}</ref>
-These data were the first to genetically implicate CRY as a component of the input pathway or the chemical-based pathway of magnetoreception. Applying these findings to his work with the monarch, Reppert has shown that both monarch CRY1 and CRY2 proteins, when transgenically expressed in CRY-deficient flies, successfully restore magnetoreception function. These results propose the presence of a CRY-mediated magnetosensitivity system in monarchs that may act in concordance with the sun compass to aid navigation. In 2011, Reppert also discovered that human CRY2 can substitute as a functional magnetoreceptor in CRY-deficient flies, a discovery that warrants additional research into magnetosensitivity in humans.<ref>{{cite journal |doi=10.1038/ncomms1364 |title=Human cryptochrome exhibits light-dependent magnetosensitivity |year=2011 |last1=Foley |first1=Lauren E. |last2=Gegear |first2=Robert J. |last3=Reppert |first3=Steven M. |journal=Nature Communications |volume=2 |pages=356– |pmid=21694704 |pmc=3128388 |issue=6}}</ref><ref>{{cite news |title=Insects that put Google Maps to shame |author=Matt Ridley |url=https://www.wsj.com/articles/SB10001424127887323375204578269963079963082 |newspaper=Wall Street Journal |date=February 1, 2013 |accessdate=September 28, 2013 }}</ref>
 ===Monarch butterfly migration===
-Since 2002, Reppert and coworkers have pioneered the study of the biological basis of [[monarch butterfly]] migration.<ref name="pmid19591650">{{cite journal |doi=10.1186/jbiol153 |title=Clocks, cryptochromes and Monarch migrations |year=2009 |last1=Kyriacou |first1=Charalambos P |journal=Journal of Biology |volume=8 |issue=6 |pages=55 |pmid=19591650 |pmc=2737371}}</ref><ref name="pmid20627420">{{cite journal |doi=10.1016/j.tins.2010.04.004 |title=Navigational mechanisms of migrating monarch butterflies |year=2010 |last1=Reppert |first1=Steven M. |last2=Gegear |first2=Robert J. |last3=Merlin |first3=Christine |journal=Trends in Neurosciences |volume=33 |issue=9 |pages=399–406 |pmid=20627420 |pmc=2929297}}</ref> Each fall, millions of monarchs from the eastern United States and southeastern Canada migrate as much as 4,000&nbsp;km to overwinter in roosts in Central Mexico.<ref name="pmid20627420"/>   Monarch migration is not a learned activity, given that migrants flying south are at least two generations removed from the previous year's migrants.<ref>{{cite journal |pmid=9317405 |year=1996 |last1=Brower |first1=L |author-link=Lincoln Brower|title=Monarch butterfly orientation: Missing pieces of a magnificent puzzle |volume=199 |issue=1 |pages=93–103 |journal=The Journal of Experimental Biology}}</ref> Thus, migrating monarchs must have some genetically based navigational mechanism.
+Since 2002, Reppert and coworkers have pioneered the study of the biological basis of [[monarch butterfly]] migration.<ref name="pmid19591650">{{cite journal |doi=10.1186/jbiol153 |title=Clocks, cryptochromes and Monarch migrations |year=2009 |last1=Kyriacou |first1=Charalambos P |journal=Journal of Biology |volume=8 |issue=6 |pages=55 |pmid=19591650 |pmc=2737371 |doi-access=free }}</ref><ref name = "pmid26473314">{{cite journal |doi=10.1146/annurev-ento-010814-020855 |title= Neurobiology of Monarch Butterfly Migration |year=2016 |last1=Reppert |first1=Steven M. | last2= Guerra |first2=Patrick A.| last3=Merlin |first3=Christine |journal=Annual Review of Entomology |volume=61 |pages=25–42 |pmid=26473314|doi-access=free }}</ref> Each fall, millions of monarchs from the eastern United States and southeastern Canada migrate as much as 4,000&nbsp;km to overwinter in roosts in Central Mexico.<ref name="pmid20627420">{{cite journal|year=2010 |last1=Reppert|first1=Steven M. |last2 =Gegear |first2= Robert J. |last3=Merlin|first3=Christine|title=Navigational mechanisms of migrating monarch butterflies |volume=33 |issue=9 |pages=399–406 |journal=Trends in Neurosciences|doi=10.1016/j.tins.2010.04.004 | pmid=20627420|pmc=2929297 }}</ref>  Monarch migration is not a learned activity, given that migrants flying south are at least two generations removed from the previous year's migrants.<ref>{{cite journal |pmid=9317405 |year=1996 |last1=Brower |first1=L |author-link=Lincoln Brower|title=Monarch butterfly orientation: Missing pieces of a magnificent puzzle |volume=199 |issue=1 |pages=93–103 |journal=The Journal of Experimental Biology|doi=10.1242/jeb.199.1.93 |doi-access=free }}</ref> Thus, migrating monarchs must have some genetically based navigational mechanism.
-Reppert and colleagues have focused on a novel [[circadian clock]] mechanism and its role in time-compensated sun compass orientation, a major navigational strategy that butterflies use during their fall migration.<ref name="pmid20627420"/> Using clock-shift experiments, they showed that the circadian clock must interact with the sun compass to enable migrants to maintain a southerly flight direction as the sun moves daily across the sky.<ref>{{cite journal |doi=10.1126/science.1084874 |title=Illuminating the Circadian Clock in Monarch Butterfly Migration |year=2003 |last1=Froy |first1=O. |journal=Science |volume=300 |issue=5623 |pages=1303–5 |pmid=12764200 |last2=Gotter |first2=AL |last3=Casselman |first3=AL |last4=Reppert |first4=SM}}</ref>
+Reppert and colleagues have focused on a novel [[circadian clock]] mechanism and its role in time-compensated sun compass orientation, a major navigational strategy that butterflies use during their fall migration.<ref name="pmid20627420"/> Using clock-shift experiments, they showed that the circadian clock must interact with the sun compass to enable migrants to maintain a southerly flight direction as the sun moves daily across the sky.<ref>{{cite journal |doi=10.1126/science.1084874 |title=Illuminating the Circadian Clock in Monarch Butterfly Migration |year=2003 |last1=Froy |first1=O. |journal=Science |volume=300 |issue=5623 |pages=1303–5 |pmid=12764200 |last2=Gotter |first2=AL |last3=Casselman |first3=AL |last4=Reppert |first4=SM|bibcode=2003Sci...300.1303F |s2cid=12011719 }}</ref> Reppert collaborated with Eli Shlizerman at the University of Washington and Daniel Forger at the University of Michigan to propose a working mathematical model of the time-compensated sun compass.<ref>{{cite journal |doi=10.1016/j.celrep.2016.03.057 |title=Neural Integration Underlying a Time-Compensated Sun Compass in the Migratory Monarch Butterfly |year=2016 |last1=Shlizerman |first1=E |journal=Cell Reports |volume=15 |issue=4 |pages=683–91 |pmid=27149852 |pmc=5063661 |last2=Phillips-Portillo |first2=J|last3=Forger |first3=DB |last4=Reppert |first4=SM}}</ref>
 ====Clockwork mechanism====
-The monarch clockwork model, which has both ''Drosophila''-like and mammal-like aspects, is unique because it employs two distinct CRY proteins. As presented in a 2010 review paper,<ref name="pmid20627420"/> the clock mechanism, on a gene/protein level, operates as follows:
+The monarch clockwork model, which has both ''Drosophila''-like and mammal-like aspects, is unique because it employs two distinct CRY proteins. As presented in a review article,<ref name = "pmid26473314"/> the clock mechanism, on a gene/protein level, operates as follows:
-* In an autoregulatory transcriptional feedback loop, heterodimers of CLOCK (CLK) and CYCLE (CYC) form and drive the transcription of the ''Per'', Tim'', and ''Cry2'' genes.
+* In an autoregulatory transcriptional feedback loop, heterodimers of CLOCK (CLK) and CYCLE (CYC) form and drive the transcription of the ''Per'', ''Tim'', and ''Cry2'' genes.
 * TIM, PER, and CRY2 proteins are translated and form complexes in the cytoplasm.
 * 24 hours later, CRY2 returns to the nucleus and inhibits CLK:CYC transcription.
@@ Line 104: / Line 100: @@
 ====Antennal clocks====
-Reppert’s lab expanded upon [[Fred Urquhart|Fred Urquhart's]] postulation that antennae play a role in monarch migration. In 2009 Reppert’s lab reported that, despite previous assumptions that the time-compensation clocks are located exclusively in the brain, there are also clocks located in the antennae, which "are necessary for proper time-compensated sun compass orientation in migratory monarch butterflies.”<ref name=Reppert_2009>{{cite journal |doi=10.1126/science.1176221 |title=Antennal Circadian Clocks Coordinate Sun Compass Orientation in Migratory Monarch Butterflies |year=2009 |last1=Merlin |first1=C. |last2=Gegear |first2=R. J. |last3=Reppert |first3=S. M. |journal=Science |volume=325 |issue=5948 |pages=1700–4 |pmid=19779201 |pmc=2754321}}</ref>  They concluded this by comparing the sun compass orientation of monarch migrants with intact antennae and those whose antennae had been removed.<ref name="Reppert_2009"/> Reppert's lab also studied antennae in vitro and found that antennal clocks can be directly entrained by light and can function independently from the brain.<ref name="Reppert_2009"/> Further research is needed, however, on the interaction between the circadian clocks in monarch butterfly's antennae and the sun compass in the brain.
+Reppert’s lab expanded upon [[Fred Urquhart|Fred Urquhart's]] postulation that antennae play a role in monarch migration. In 2009 Reppert and coworkers Christine Merlin and Robert Gegear reported that, despite previous assumptions that the time-compensation clocks are located exclusively in the brain, there are also clocks located in the antennae, which "are necessary for proper time-compensated sun compass orientation in migratory monarch butterflies.”<ref name=Reppert_2009>{{cite journal |doi=10.1126/science.1176221 |title=Antennal Circadian Clocks Coordinate Sun Compass Orientation in Migratory Monarch Butterflies |year=2009 |last1=Merlin |first1=C. |last2=Gegear |first2=R. J. |last3=Reppert |first3=S. M. |journal=Science |volume=325 |issue=5948 |pages=1700–4 |pmid=19779201 |pmc=2754321|bibcode=2009Sci...325.1700M }}</ref>  They concluded this by comparing the sun compass orientation of monarch migrants with intact antennae and those whose antennae had been removed.<ref name="Reppert_2009"/> Reppert's lab also studied antennae in vitro and found that antennal clocks can be directly entrained by light and can function independently from the brain.<ref name="Reppert_2009"/> Further research is needed, however, on the interaction between the circadian clocks in monarch butterfly's antennae and the sun compass in the brain.
-In 2012, Reppert and colleagues determined that only a single antenna is sufficient for sun compass orientation. They did so by painting one antenna black to cause discordant light exposure between the two antennae; the single not-painted antenna was sufficient for orientation. All four clock genes (''per'', ''tim'', ''cry1'', and ''cry2'') were expressed in the various studied areas of the antenna, suggesting that "light entrained circadian clocks are distributed throughout the length of the monarch butterfly antenna." <ref>{{cite journal |doi=10.1038/ncomms1965 |title=Discordant timing between antennae disrupts sun compass orientation in migratory monarch butterflies |year=2012 |last1=Guerra |first1=Patrick A. |last2=Merlin |first2=Christine |last3=Gegear |first3=Robert J. |last4=Reppert |first4=Steven M. |journal=Nature Communications |volume=3 |pages=958 |pmid=22805565 |issue=7 |pmc=3962218}}</ref>
+In 2012, Reppert and colleagues determined that only a single antenna is sufficient for sun compass orientation. They did so by painting one antenna black to cause discordant light exposure between the two antennae; the single not-painted antenna was sufficient for orientation. All four clock genes (''per'', ''tim'', ''cry1'', and ''cry2'') were expressed in the various studied areas of the antenna, suggesting that "light entrained circadian clocks are distributed throughout the length of the monarch butterfly antenna."<ref>{{cite journal |doi=10.1038/ncomms1965 |title=Discordant timing between antennae disrupts sun compass orientation in migratory monarch butterflies |year=2012 |last1=Guerra |first1=Patrick A. |last2=Merlin |first2=Christine |last3=Gegear |first3=Robert J. |last4=Reppert |first4=Steven M. |journal=Nature Communications |volume=3 |pages=958 |pmid=22805565 |issue=7 |pmc=3962218|bibcode=2012NatCo...3..958G }}</ref>
-In 2013, Reppert and colleagues showed that spring remigrants also use an antenna-dependent time-compensated sun compass to direct their northward flight from Mexico to the southern United States.<ref>{{cite journal |doi=10.1016/j.cub.2013.01.052 |title=Coldness Triggers Northward Flight in Remigrant Monarch Butterflies |year=2013 |last1=Guerra |first1=Patrick A. |last2=Reppert |first2=Steven M. |journal=Current Biology |volume=23 |issue=5 |pages=419–23 |pmid=23434279}}</ref>
+In 2013, Reppert and Patrick Guerra showed that spring remigrants also use an antenna-dependent time-compensated sun compass to direct their northward flight from Mexico to the southern United States.<ref>{{cite journal |doi=10.1016/j.cub.2013.01.052 |title=Coldness Triggers Northward Flight in Remigrant Monarch Butterflies |year=2013 |last1=Guerra |first1=Patrick A. |last2=Reppert |first2=Steven M. |journal=Current Biology |volume=23 |issue=5 |pages=419–23 |pmid=23434279|doi-access=free |bibcode=2013CBio...23..419G }}</ref>
 ====Sun compass====
-Using anatomical and electrophysiological studies of the monarch butterfly brain, Reppert and colleagues have indicated that the central complex, a midline structure in the central brain, is likely the site of the sun compass.<ref>{{cite journal |doi=10.1002/cne.23214 |title=Anatomical basis of sun compass navigation II: The neuronal composition of the central complex of the monarch butterfly |year=2013 |last1=Heinze |first1=Stanley |last2=Florman |first2=Jeremy |last3=Asokaraj |first3=Surainder |last4=El Jundi |first4=Basil |last5=Reppert |first5=Steven M. |journal=Journal of Comparative Neurology |volume=521 |issue=2 |pages=267–98 |pmid=22886450}}</ref>
+Using anatomical and electrophysiological studies of the monarch butterfly brain, Stanley Heinze working in Reppert’s lab provided evidence that the central complex, a midline structure in the central brain, is likely the site of the sun compass.<ref>{{cite journal |doi=10.1002/cne.23214 |title=Anatomical basis of sun compass navigation II: The neuronal composition of the central complex of the monarch butterfly |year=2013 |last1=Heinze |first1=Stanley |last2=Florman |first2=Jeremy |last3=Asokaraj |first3=Surainder |last4=El Jundi |first4=Basil |last5=Reppert |first5=Steven M. |journal=Journal of Comparative Neurology |volume=521 |issue=2 |pages=267–98 |pmid=22886450|s2cid=205682692 }}</ref>
+====Magnetic compass====
+Reppert and colleagues Patrick Guerra and Robert Gegear showed that migratory monarchs can use a light-dependent, inclination-based, magnetic compass for navigation on overcast days.<ref>{{cite journal |doi=10.1038/ncomms5164 |title=A magnetic compass aids monarch butterfly migration |year=2014 |last1=Guerra |first1=Patrick A. |last2=Gegear |first2=Robert J. |last3=Reppert |first3=Steven M. |journal=Nature Communications |volume=5 |pages=4164 |pmid=24960099|pmc=4090716 |bibcode=2014NatCo...5.4164G }}</ref> Genetic studies from Christine Merlin’s laboratory show that the photoreceptive CRY1 protein is essential for the monarch’s light-sensitive magnetic compass.<ref>{{cite journal |doi=10.1038/s41467-021-21002-z |title=Cryptochrome 1 mediates light-dependent inclination magnetosensing in monarch butterflies. |year=2021 |last1=Wan |first1=Guijun |last2=Hayden |first2=Ashley N. |last3=Iams |first3=Samanatha E. | last4=Merlin|first4=Christine |journal=Nature Communications |volume=12|issue=1 |pages=771 |doi-access=free |pmid=33536422 |pmc=7859408 |bibcode=2021NatCo..12..771W }}</ref> The successful use of reverse genetics in monarchs would indicate that the butterfly is an excellent choice for helping to delineate the molecular mechanism underlying light-dependent magnetosensing in the context of compass navigation.
 ====Temperature====
-Reppert and coworkers showed that fall migrants prematurely exposed to overwintering-like coldness reverse their flight orientation to the north. The temperature microenvironment at the overwintering site is essential for successful completion of the migration cycle: without cold exposure, aged migrants continue to orient to the south. The discovery that coldness triggers the northward flight direction in spring remigrants underscores how vulnerable the migration may be to climate change.<ref>{{cite news |title=Climate change may disrupt monarch butterfly migration |author=Nayantara Narayanan |author2=ClimateWire |url=http://www.scientificamerican.com/article.cfm?id=climate-change-may-disrupt-monarch-butterfly-migration |newspaper=Scientific American |date=February 22, 2013 |accessdate=September 28, 2013}}</ref><ref>{{cite news |title=Chill turns monarchs north |author=Meghan Rosen |url=http://www.sciencenews.org/view/generic/id/348485/description/Chill_turns_monarchs_north |newspaper=ScienceNews |date=March 23, 2013 |accessdate=September 28, 2013 }}</ref>
+Reppert and Patrick Guerra showed that fall migrants prematurely exposed to overwintering-like coldness reverse their flight orientation to the north. The temperature microenvironment at the overwintering site is essential for successful completion of the migration cycle: without cold exposure, aged migrants continue to orient to the south. The discovery that coldness triggers the northward flight direction in spring remigrants underscores how vulnerable the migration may be to climate change.<ref>{{cite news |title=Climate change may disrupt monarch butterfly migration |author=Nayantara Narayanan |author2=ClimateWire |url=http://www.scientificamerican.com/article.cfm?id=climate-change-may-disrupt-monarch-butterfly-migration |newspaper=Scientific American |date=February 22, 2013 |accessdate=September 28, 2013}}</ref><ref>{{cite news |title=Chill turns monarchs north |author=Meghan Rosen |url=http://www.sciencenews.org/view/generic/id/348485/description/Chill_turns_monarchs_north |newspaper=ScienceNews |date=March 23, 2013 |accessdate=September 28, 2013 |archive-date=October 2, 2013 |archive-url=https://web.archive.org/web/20131002070324/http://www.sciencenews.org/view/generic/id/348485/description/Chill_turns_monarchs_north |url-status=dead }}</ref>
 ====Monarch butterfly genome====
-In 2011, Reppert and colleagues presented the draft sequence of the monarch butterfly genome and a set 16,866 protein-coding genes. This is the first characterized genome of a butterfly and of a long-distance migratory species.<ref>{{cite journal |doi=10.1016/j.cell.2011.09.052 |title=The Monarch Butterfly Genome Yields Insights into Long-Distance Migration |year=2011 |last1=Zhan |first1=Shuai |last2=Merlin |first2=Christine |last3=Boore |first3=Jeffrey L. |last4=Reppert |first4=Steven M. |journal=Cell |volume=147 |issue=5 |pages=1171–85 |pmid=22118469 |pmc=3225893}}</ref><ref>{{cite journal |doi=10.1016/j.cell.2011.11.009 |title=A Genome Befitting a Monarch |year=2011 |last1=Stensmyr |first1=Marcus C. |last2=Hansson |first2=Bill S. |journal=Cell |volume=147 |issue=5 |pages=970–2 |pmid=22118454}}</ref><ref>
+In 2011, Reppert and colleagues presented the draft sequence of the monarch butterfly genome and a set 16,866 protein-coding genes. This is the first characterized genome of a butterfly and of a long-distance migratory species.<ref>{{cite journal |doi=10.1016/j.cell.2011.09.052 |title=The Monarch Butterfly Genome Yields Insights into Long-Distance Migration |year=2011 |last1=Zhan |first1=Shuai |last2=Merlin |first2=Christine |last3=Boore |first3=Jeffrey L. |last4=Reppert |first4=Steven M. |journal=Cell |volume=147 |issue=5 |pages=1171–85 |pmid=22118469 |pmc=3225893}}</ref><ref>{{cite journal |doi=10.1016/j.cell.2011.11.009 |title=A Genome Befitting a Monarch |year=2011 |last1=Stensmyr |first1=Marcus C. |last2=Hansson |first2=Bill S. |journal=Cell |volume=147 |issue=5 |pages=970–2 |pmid=22118454|doi-access=free }}</ref><ref>
 {{Cite news
   | last = Johnson
@@ Line 130: / Line 129: @@
 In 2012, Reppert and colleagues established [http://monarchbase.umassmed.edu/ MonarchBase], an integrated database for the genome of ''Danaus plexippus''. The goal of the project was to make genomic and proteomic information about monarch butterflies accessible to biological and lepidopteran communities.<ref>{{cite journal |doi=10.1093/nar/gks1057 |title=MonarchBase: The monarch butterfly genome database |year=2012 |last1=Zhan |first1=S. |last2=Reppert |first2=S. M. |journal=Nucleic Acids Research |volume=41 |pages=D758–63 |pmid=23143105 |issue=Database issue |pmc=3531138}}</ref>
-In 2013, Reppert and coworkers developed a novel gene-targeting approach in monarchs that uses a zinc finger nuclease strategy to define the essential nature of CRY2 for clockwork function in lepidopterans.<ref>{{cite journal |doi=10.1101/gr.145599.112 |title=Efficient targeted mutagenesis in the monarch butterfly using zinc-finger nucleases |year=2012 |last1=Merlin |first1=C. |last2=Beaver |first2=L. E. |last3=Taylor |first3=O. R. |last4=Wolfe |first4=S. A. |last5=Reppert |first5=S. M. |journal=Genome Research |volume=23 |pages=159–68 |pmid=23009861 |issue=1 |pmc=3530676}}</ref> Targeted mutagenesis of ''Cry2'' indeed resulted in the in vivo disruption of circadian behavior and the molecular clock mechanism. The ZFN strategy is a powerful tool for targeting additional clock genes in monarchs and other members of Lepidoptera.
+In 2013, Christine Merlin and Scot Wolfe developed in Reppert’s lab a novel gene-targeting approach in monarchs that uses a zinc finger nuclease strategy to define the essential nature of CRY2 for clockwork function in lepidopterans.<ref>{{cite journal |doi=10.1101/gr.145599.112 |title=Efficient targeted mutagenesis in the monarch butterfly using zinc-finger nucleases |year=2012 |last1=Merlin |first1=C. |last2=Beaver |first2=L. E. |last3=Taylor |first3=O. R. |last4=Wolfe |first4=S. A. |last5=Reppert |first5=S. M. |journal=Genome Research |volume=23 |pages=159–68 |pmid=23009861 |issue=1 |pmc=3530676|url=https://kuscholarworks.ku.edu/bitstream/1808/13434/1/Merlin%20et%20al.%20-%202013%20-%20Efficient%20targeted%20mutagenesis%20in%20the%20monarch%20butterfly%20using%20zinc-finger%20nucleases.pdf }}</ref> Targeted mutagenesis of ''Cry2'' indeed resulted in the in vivo disruption of circadian behavior and the molecular clock mechanism. Further work in Merlin’s lab has shown that nuclease strategies are powerful tools for targeting additional clock genes in monarchs and altering gene function.<ref>{{cite journal |doi=10.1534/g3.116.027029 |title=Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis |year=2016|last1=Markert |first1=Matthew J. |last2=Zhang |first2=Ying|last3=Enuameh | first3=Metewo S. | last4=Reppert |first4=Steven M.| last5=Wolfe |first5=Scot A. | last6= Merlin|first6=Christine |journal=G3 (Bethesda) |volume=6 |issue=4 |pages=905–15 |pmid=26837953 |pmc=4825660}}</ref>
+In 2016, Reppert collaborated with Marcus Kronforst at the University of Chicago and others to use population genetic studies to define the evolutionary history of the monarch migration.<ref>{{cite journal |doi=10.1038/nature13812 |title=The genetics of monarch butterfly migration and warning colouration |year=2014 |last1=Zhan |first1=Shuai |last2=Zhang |first2=Wei |last3=Niitepõld |first3=Kristjan |last4=Hsu |first4=Jeremy |last5=Fernández Haeger |first5=Juan |last6=Zalucki |first6=Myron P. |last7=Altizer |first7=Sonia |last8=de Roode |first8=Jacobus C. |last9=Reppert |first9=Steven M. |last10=Kronforst |first10= Marcus R. |journal=Nature |volume=514 |issue=7522 |pages=317–21 |pmid=25274300|pmc=4331202 |bibcode=2014Natur.514..317Z }}</ref>
+==Awards and honors==
+* Charles King Trust Research Fellowship, 1981–1984
+* Basil O'Connor Starter Scholar Research Award, March of Dimes Fund, 1981–1983
+* Established Investigator Award of the [[American Heart Association]], 1985–1990
+* Fellow, American Society for Clinical Investigation, elected 1987
+* [[E. Mead Johnson Award]] for Outstanding Research, 1989<ref>{{cite web |url=http://www.aps-spr.org/spr/Awards/EMJ.htm |title=SPR Member Info |access-date=2010-08-30 |url-status=dead |archive-url=https://web.archive.org/web/20100822075701/http://www.aps-spr.org/SPR/Awards/EMJ.htm |archive-date=2010-08-22 }}</ref>
+* NIH-NICHD MERIT Award, 1992–2002
+* Honorary master's degree, [[Harvard University]], 1993
+* Higgins Family Professor of Neuroscience, University of Massachusetts Medical School, 2001–2017
+* President, Society for Research on Biological Rhythms, 2004
+* Fellow of the American Association for the Advancement of Science, elected 2011<ref>{{Cite web | url=http://www.aaas.org/aboutaaas/fellows/ |title = AAAS Honorary Fellows}}</ref>
+* Gregor J. Mendel Honorary Medal for Merit in the Biological Sciences from the Academy of Sciences of the Czech Republic, 2012<ref>{{cite web|last=Czech News Agency (ČTK)|title=Academy of Science awards American researcher Reppert|url=http://praguemonitor.com/2013/03/21/academy-science-awards-american-researcher-reppert|publisher=Prague Daily Monitor}}</ref>
+* Honorary doctorate, University of South Bohemia, Czech Republic, 2013<ref>{{cite web|title=Neurobiolog Steven M. Reppert převzal čestný doktorát Jihočeské univerzity|url=http://www.jcu.cz/news/neurobiolog-steven-m.-reppert-ziskal-cestny-doktorat-jihoceske-univerzity|publisher=University of South Bohemia}}</ref>
+* Chancellor’s Medal for Distinguished Scholarship, University of Massachusetts Medical School, 2016<ref>
+{{Cite news
+  | last = Larson
+  | first = Lisa M.
+  | title = Convocation 2016 recognizes Chancellor's Medal recipients; faculty invested as named chairs
+  | newspaper = UMassMedNOW
+  | location = Worcester, MA
+  | date = 14 September 2016
+  | url = https://umassmed.edu/news/news-archives/2016/09/convocation-2016-recognizes-chancellors-medal-recipients-faculty-invested-as-named-chairs/
+  | accessdate = 16 June 2019}}</ref>
 == References ==
@@ Line 137: / Line 162: @@
 == External links ==
 * [http://reppertlab.org/ Reppert Lab website]
-* [http://profiles.umassmed.edu/profiles/ProfileDetails.aspx?From=SE&Person=622 UMass Medical School faculty page]
+* [https://profiles.umassmed.edu/display/133192 UMass Medical School faculty page]
-*{{PubMedAuthorSearch|Reppert|SM}}
+* {{PubMedAuthorSearch|Reppert|SM}}
+* {{Google Scholar id |id=IDUsWwIAAAAJ }}
 * [http://monarchbase.umassmed.edu/ MonarchBase]
-* [https://www.ibiology.org/ibioseminars/steven-m-reppert-part-1.html Steven Reppert Seminar: Neurobiology of Monarch Butterfly Migration]
+* [https://www.ibiology.org/ecology/butterfly-migration/ Steven Reppert Seminar: Neurobiology of Monarch Butterfly Migration]
 {{Authority control}}
@@ Line 147: / Line 173: @@
 [[Category:Living people]]
 [[Category:American neuroscientists]]
-[[Category:University of Massachusetts Medical School faculty]]
+[[Category:UMass Chan Medical School faculty]]
 [[Category:1946 births]]
 [[Category:Chronobiologists]]

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