Jump to content

Steven M. Reppert

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Jcfoster1991 (talk | contribs) at 06:25, 25 April 2013 (→Mammalian Melatonin Receptors). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Steven M. Reppert is an American neuroscientist who is known for his contributions to the fields of circadian biology and neuroethology. His research has focused largely 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 currently the founding chair of the Department of Neurobiology and the Higgins Family Professor of Neuroscience at the University of Massachusetts Medical School.

Background

Steven Reppert was born on September 4, 1946 in Sioux city, IA. 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 1973-1976 he did an internship and residency in Pediatrics at the Massachusetts General Hospital. From 1976-79 Reppert was a posdoctoral fellow in Link lneuroendocrinology 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.[1] 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.[2]

Reppert was a Charles King Trust Research Fellow from 1981 to 1983 and an Established Investigator of the American Heart Association from 1985 to 1990. He has been a recipient of the E. Mead Johnson Award for Outstanding Research Contributions (1989)[3] and the NIH-NICHD MERIT Award (1992–2002). From 2002 to 2004, he served as president of the Society for Research on Biological Rhythms.[4] He is an elected fellow of the American Association for the Advancement of Science.[5] Reppert has published more than 150 papers in peer-reviewed journals and is the principal inventor on seven patents derived from his research.[6]

Research

Fetal Circadian Clocks

Based on studies conducted in rodents, the suprachiasmatic nucleus is functional in the fetus before the fetal brain is capable of registering the presence of light. Reppert and colleagues report that the fetal SCN is entrained to the light-dark cycle before the retinohypothalamic pathway innervates the SCN. [7] This finding indicates that the mother, and her entrainment to surrounding light-dark cycles, must provide 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.” [8]

Mammalian Circadian Clocks

Steven Reppert and colleagues have made significant contributions towards providing insight into mammalian circadian clocks.

Discovering cell autonomy in the SCN

Reppert and colleagues discovered that the SCN, the mammalian circadian clock mechanism contains a large population of autonomous, single-cell circadian oscillators.[9] He cultured cells from neonatal rat SCN on fixed Microelectrode array that allowed him to monitor individual Neuron activity in culture. From this he saw that circadian rhythms expressed by neurons in the same culture were not synchronized.

Defining function of clock genes in mice: PERIOD2 and PERIOD3

Reppert also discovered the mammalian clock genes mPer2 and mPer3 as well as defined their function. He found that the PER2 and PER3 proteins as well as the previously discovered PER1 protein share several regions of Homology with each other and Drosophila PER, including the presence of a PAS domain.[10] [11] Reppert found different light responses among the three Per genes.[12] Unlike mPer1 and mPer2 RNA levels, mPer3 RNA levels are not acutely altered by light exposure during the subjective night. He also found that mPer3 is widely expressed in tissues outside of the brain including the liver, skeletal muscles, and testis. To determine the function of Per1, 2, and 3, Reppert and colleagues disrupted the three genes.[13] They found that mice without mPer1 or mPer2 had altered locomotor activity rhythms in constant darkness. They also found that clock gene RNA rhythms were altered in mice lacking mPer2 but not mPer1-deficient mice. Looking at double-mutant mice lacking mPer1 and mPer3 and mice lacking mPer2 and mPer3, they found that behavior rhythms were similar to mice lacking just mPer1 or mPer2. This confirmed that mPer3 functions outside the core circadian clockwork. Removing mPer1 and mPer2, they found that both genes together were necessary for rhythmicity. Overall, Reppert helped discover that mPER1 influences rhythmicity through interaction with other clock proteins while mPER2 is involved in positively regulating rhythmic gene expression.

Defining the 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) and Translation (genetics) feedback loops.[14] They proposed three interacting molecular loops. The first loop involves cryptochrome. They proposed that there is an auto-regulatory negative feedback loop for mCry where mCRY protein negatively influences mCry gene transcription. The second loop involves mPer and CCGs like Vasopressin. This loop is driven by the CLOCK:BMAL1 protein dimer, but is turned off by mPer and CCG gene products. In this loop mCRY acts as a negative regulator while mPER2 drives transcription of the Bmal1 gene. In addition, mPER1 acts in protein stabilization and CCG products function as output signals. The third loop involves the rhythmic regulation of Bmal1. Rhythmicity of Bmal1 is controlled by the presence and absence of mPER2 which acts to drive transcription.

CLOCK and NPAS2

Reppert found a new and unexpected role for NPAS2.[15] He discovered that CLOCK and NPAS2 have overlapping roles in the SCN. Reppert and colleagues observed that CLOCK-deficient mice continued to have behavioral and molecular rhythms, albeit slightly shorter than wild-type mice. This showed that CLOCK was not essential for circadian rhythm in locomotor activity in mice. They then discovered that NPAS2 is a Paralog of CLOCK and can functionally substitute CLOCK by dimerizing with BMAL1. This was discovered by investigating CLOCK deficient mice. CLOCK-deficient mice with one normal Npas2 allele had a shortened period in constant darkness while CLOCK deficient mice without the Npas2 allele were arrhythmic. Finally, Reppert and Colleagues discovered that circadian rhythms in peripheral oscillators require CLOCK.[16] This was discovered by investigating CLOCK deficient, NPAS2-deficient, and double-mutant mice. After monitoring bioluminescent rhythms of peripheral tissues in culture, they found that these tissues were arrhythmic without CLOCK. Thus, there is a fundamental difference between CLOCK and NPAS2.

Mammalian Melatonin Receptors

In 1994, Reppert cloned human and sheep Mel1a melatonin receptors, a family of GPCRs that bind the pineal hormone melatonin, and utilized in situ hybridization to localize their expression in the mammalian brain to the suprachiasmatic nucleus (SCN) and hypophyseal pars tuberalis[17] . The Mel1a receptor is believed to be responsible for circadian reproductive actions of seasonal breeding mammals [17].

In 1995 Reppert was involved in the cloning and characterization of the Mel1b melatonin receptor. He found that the receptor was predominantly expressed in the retina where it is believed modify light light-dependent retinal functions [18]. The Mel1b receptor was shown to have similar binding and functional characteristics to those of Mel1a and was also expressed in the brain to a lesser extent, entailing that it too may participate in the circadian and reproductive actions of melatonin [18]. However, Reppert identified outbred populations of Syrian hamsters lacking functional Mel1b receptors that still maintained circadian and reproductive responses to melatonin [19]; these data indicate that the Mel1b receptor is not necessary for the circadian and reproductive actions of melatonin.

In 1997 Reppert participated in identification of melatonin receptor involvement in two distinct effects of melatonin on the mammalian SCN, acute neuronal inhibition and phase-shifting. Reppert showed that the Mel1a receptor was necessary for melatonin induced acute inhibitory action on the SCN [20]. However the Mel1a receptor was not shown to be necessary phase shifting effects of melatonin on the SCN as disruption of the Mel1a receptor altered, but did not eliminate the SCN phase shifting response [20]. The latter observance implicated the Mel1b receptor, which is expressed at low levels in the SCN, as another receptor candidate in melatonin-induced phase shifts of the SCN.

Cryptochrome Research

In 2003, Steven Reppert began investigating the functional and evolutionary properties of the cryptochrome (CRY) protein in the Monarch Butterfly. Reppert identified two Cry genes in the Monarch, dsCry1 and dsCry2 [21]. His work demonstrated that dsCRY1 is functionally analogous to dCRY, the blue light photoreceptor necessary for photoentrainment in Drosophila. He also demonstrated that dsCRY2 was functionally analogous to mCRY in vertebrates, acting as a transcriptional repressor in the circadian clock transcriptional translation feedback loop. These data propose the existence of a novel circadian clock unique to non-drosophilid insects that possess mechanisms characteristic of both drosophilian and mammalian clocks[22]. His research also identified a dsCry2 mRNA positive neural circuit that synapses at the central complex, the perceived site of the sun compass in monarchs, implying that dsCry2 may mediate the internal circadian clock component of monarch navigation [23].

In 2008, Reppert discovered the necessity of dCry for light-dependent magnetoreception responses in Drosophila. He also showed that magnetoreception requires UVA/blue light, the spectrum corresponding with the action spectrum of dCRY [24]. These data were the first to involve Cry as a component of the input pathway or the chemical-based pathway of magnetoreception. Applying these finding to his work with the monarch, Reppert has shown that both Monarch dsCRY1 and dsCRY2 proteins, when transgenically expressed in cry° 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 clock to aid navigation. In 2011, Reppert also discovered that hCry2 can substitute as a functional magnetoreceptor in Cry deficient flies, a discovery that warrants additional research into magnetosensitivity in humans and possible influences of magnetic fields on human visual function These results propose the presence of a Cry-mediated magnetosensitivity system in monarchs that may act in concordance with the sun clock to aid navigation. In 2011, Reppert also discovered that hCry2 can substitute as a functional magnetoreceptor in Cry deficient flies, a discovery that warrants additional research into magnetosensitivity in humans and possible influences of magnetic fields on human visual function [25].

Monarch Butterfly Migration Research

Background

Since 2002, Reppert and co-workers have pioneered the study of the biological basis of monarch butterfly migration.[26][27] Each fall, millions of monarchs from Eastern United States and Southeastern Canada migrate over 4000km to overwinter in roosts in Central Mexico.[28] Previous research has found that monarch migration is not a learned activity since migrants going south are at least two generations removed from previous generations of migrants.[29] Thus, monarch migration must have some biological basis that aids navigation.

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, first described by Karl von Frisch in 1967 in foraging honeybees and by Gustav Kramer in 1957 in migratory birds. Monarch butterflies must re-calibrate their navigation using environmental factors. Their circadian clock is standardized to local time by dawn and dusk while their Sun compass may be calibrated by geomagnetic forces, visualizing certain landmarks, barometric pressure, and prevailing wind direction.[30]

Reppert and colleagues have pioneered research demonstrating the importance of the circadian clock in regulating the time-compensated component of flight orientation. Reppert and colleagues conducted a clock-shift experiment to demonstrate how the circadian clock interacts with the Sun compass in order to enable migrants to maintain a southwesterly flight direction as the Sun moves daily.[31] They exposed one group of migrants to 12 hours of light from 7:00AM to 7:00PM, a standard fall lighting schedule, followed by 12 hours of darkness. They exposed another group to 12 hours of light 6 hours earlier between 1:00AM and 1:00PM. Using an outdoor flight simulator with the migrants tethered, they found that the migrants with the standard light schedule oriented southwest as expected, while the migrants exposed to a light schedule 6 hours earlier oriented to the southeast, demonstrating a circadian shift in the time-compensated sun compass. Reppert and colleagues then exposed the previous migrant groups to constant light, which is known to disrupt circadian timing, in order to test if the circadian clock is necessary for successful migration. They found no difference in orientation direction between migrants exposed to the standard light schedule and those exposed to an earlier light schedule; this finding indicated a loss of circadian control and demonstrated that a functioning circadian clock is necessary for successful orientation (and consequently migration) in Danaus plexippus.

Repperts lab has also provided new information on the sunlight-dependent parameters used for navigation.[32] He found that Monarch butterflies utilize patterns of Polarized light as a sun compass cue in a time-compensated manner. Using tethered migrant butterflies in an outdoor flight simulator, Reppert found that the orientation of flight was dependent on the angle of polarized light. This significant finding provides insight into how migrating monarchs can navigate under various atmospheric conditions. Reppert and others have found that the detection of polarized light relevant for flight orientation is mediated through ultraviolet Opsin-expressing Photoreceptor in the dorsal rim area of the monarch eye.[33][34]

Detailed Findings regarding Monarch Butterflies time-compensated sun compass

Steven Reppert's lab has published numerous papers detailing their findings:

  • Using previous electrophysiological studies of locusts, as well as careful mapping of the monarch butterflies brain, Reppert has indicated that the “central complex (CX) is likely the site of the actual sun compass.” [35]
  • Reppert’s lab expanded upon the previous postulations of Fred Urquhart which stated that antennae may play a role in monarch migration. In 2009 Reppert’s lab reported that, despite previous assumptions that the clock is located in the brain, there actually are antennal clocks, and “the antennae are necessary for proper time-compensated sun compass orientation in migratory monarch butterflies.” [36] They concluded this by comparing the sun compass orientation of monarch migrants with intact antennae and those whose antennae had been removed.[37] They found that migrants with intact antennae oriented southwest as expected, while those missing antennae showed disoriented group flight, leading to their findings that antennae are necessary for time-compensated sun compass orientation. Reppert's lab studied the antennae in vitro and found that these antennal clocks can be directly entrained by light that can function independently from the brain.[38] Further research is needed though on the synchronization between the circadian clocks in monarch butterfly's antennae and brain.
  • Studies of antennal clocks were expanded upon in 2012, concluding that only a single antenna is sufficient for sun compass orientation. They demonstrated this by painting a single antennae black to cause discordant light exposure between the two antennae, and found that the single not-painted antennae is still sufficient. “All four clock genes (per, tim, cry1, and cry2) were expressed in the different areas of the antennae studied, suggesting that “light entrained circadian clocks are distributed throughout the length of the monarch butterfly antenna.” [39]
  • In 2011, Reppert and colleagues presented the initial 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.[40][41][42]
  • In 2012, Reppert and colleagues established MonarchBase, an integrated database for Danaus plexippus' genome. The goal of the project was to make genomic and proteomic information about monarch butterflies accessible to biological and lepidopteran communities. [43]
  • The monarch clockwork model, which has both drosophila-like and mammalian-like aspects, is unique because it utilizes two distinct CRYPTOCHROME (CRY) proteins. As presented in a 2010 paper[44] , the clock mechanism, on a gene/protein level, operates as follows:
    • There is an autoregulatory transcription feedback loop in which heterodimers of CLOCK (CLK) and CYCLE (CYC) form and drive the transcription of the period (per) , timeless (tim), and cryptochrome2 (cry2) genes;
    • TIM (T), PER (P), and CRY2 (C2) proteins are translated and move from the nucleus to the cytoplasm where they form complexes;
    • 24 hours later CRY2 returns to the nucleus, inhibiting CLK:CYC transcription;
    • Meanwhile PER is progressively phosphorylated, which may aid CRY2 translocation into the nucleus;
    • And CRYPTOCHROME1 (CRY1, C1) protein is a circadian photoreceptor which when exposed to light, causes TIM degradation, allowing light to gain access to the central clock mechanism for photic entrainment.

References

  1. ^ "Neuroscience@NIH". NIH. Retrieved April 24, 2013.
  2. ^ http://www.umassmed.edu/neuroscience/faculty/reppert.cfm
  3. ^ http://www.aps-spr.org/spr/Awards/EMJ.htm
  4. ^ http://www.srbr.org/Pages/past_meetings.aspx
  5. ^ http://www.aaas.org/aboutaaas/fellows/
  6. ^ http://www.patentbuddy.com/Inventor/Reppert-Steven-M/1437735
  7. ^ Reppert, Steven M. (16). "Maternal Entrainment of the Developing Circadian System". Annals of the NY Academy of Sciences. 453: 162-169. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)
  8. ^ Klinkenborg, Verlyn. "Awakening to Sleep". New York Times.
  9. ^ Welsh, David (1995). "Individual Neurons Dissociated from Rat Suprachiasmatic Nucleus Express Independently Phased Circadian Firing Rhythms". Neuron. 14: 697–706. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  10. ^ Shearman, Lauren (1997). "Two period Homologs: Circadian Expression and Photic Regulation in the Suprachiasmatic Nuclei". Neuron. 19: 1261–1269. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  11. ^ Zylka, Mark (1998). "Three period Homologs in Mammals: Differential Light Responses in the Suprachiasmatic Circadian Clock and Oscillating Transcripts Outside of Brain". Neuron. 20: 1103–1110. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  12. ^ Zylka, Mark (1998). "Three period Homologs in Mammals: Differential Light Responses in the Suprachiasmatic Circadian Clock and Oscillating Transcripts Outside of Brain". Neuron. 20: 1103–1110. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  13. ^ Bae, Kiho (2001). "Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock". Neuron. 30: 525–536. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  14. ^ Shearman, Lauren (2000). "Interacting Molecular Loops in the Mammalian Circadian Clock". Science. 288: 1013–1019. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  15. ^ DeBruyne, Jason (2007). "CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock". Natural Neuroscience. 10 (5): 543–545. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  16. ^ DeBruyne, Jason (2007). "Peripheral circadian oscillators require CLOCK". Current Biology. 17: 538–539. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  17. ^ a b Reppert, Steven (October 1994). "Cloning and Characterization of a Mammalian Melatonin Receptor That Mediates Reproductive and Circadian Responses". Neuron. 13: 1177-1185. PMID 7946354. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  18. ^ a b Reppert, Steven (June 8 1995). "Molecular characterization of a second melatonin receptor expressed in human retina and brain: The Mellb melatonin receptor". Neurobiology. 92: 8734-8738. PMID 7568007. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  19. ^ Weaver, David (1996). "Nature's Knockout: The Mel1b receptor Is not necessary for reproductive and circadian responses to melatonin in Siberian Hamsters ". Molecular Endocrinology. 10 (11): 1478-1487. PMID 8923472. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  20. ^ a b Liu, Chen (July 1997). "Molecular Dissection of Two Distinct Actions of Melatonin on the Suprachiasmatic Circadian Clock". Neuron. 19: 91–102. PMID 9247266. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  21. ^ Reppert, SM (6 Dec, 2005). "The two CRYs of the butterfly". Current Biology. 15 (23): R953-R954. PMID 16332522. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: date and year (link)
  22. ^ Reppert, SM (Jan 8, 2008). "Cryptochromes Define a Novel Circadian Clock Mechanism in Monarch Butterflies That May Underlie Sun Compass Navigation". PLOS. 6 (1): e4. PMID 18184036. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  23. ^ Reppert, SM (8 Jan 2008). "Cryptochromes Define a Novel Circadian Clock Mechanism in Monarch Butterflies That May Underlie Sun Compass Navigation". PLOS. 6 (1): e4. PMID 18184036. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  24. ^ Reppert, SM (21 August 2008). "Cryptochrome mediates light-dependent magnetosensitivity in Drosophila". Nature. 454: 1014-1018. PMID 18641630. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  25. ^ Reppert, SM (21 June 2011). "Human cryptochrome exhibits light-dependent magnetosensitivity". Nature Communications. 356. 2. PMID 21694704. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  26. ^ Kyriacou CP (2009). "Clocks, cryptochromes and Monarch migrations". Journal of Biology. 8 (6): 55. doi:10.1186/jbiol153. PMC 2737371. PMID 19591650.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  27. ^ Reppert SM, Gegear RJ, Merlin C (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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  28. ^ Reppert, Steven (2010). "Navigational Mechanisms of Migrating Monarch Butterflies". Trends in Neurosciences. 33 (9): 399–406. doi:10.1016/j.tins.2010.04.004. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  29. ^ Brower, Lincoln (1996). "Monarch Butterfly Orientation: Missing Pieces of a Magnificent Puzzle". Journal of Experimental Biology. 199: 93–103.
  30. ^ Merlin, Christine (2009). "Antennal Circadian Clocks Coordinate Sun Compass Orientation in Migratory Monarch Butterflies". Science. 325 (1700–1704). doi:10.1126/science.1176221. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  31. ^ Froy, Oren (2003). "Illuminating the Circadian Clock in Monarch Butterfly Migration". Science. 300: 1303–1305. doi:10.1126/science.1084874. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  32. ^ Reppert, Steven (2004). "Polarized Light Helps Monarch Butterflies Navigate". Current Biology. 14: 155–158. doi:10.1016/j.cub.2003.12.034. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  33. ^ Reppert, Steven (2004). "Polarized Light Helps Monarch Butterflies Navigate". Current Biology. 14: 155–158. doi:10.1016/j.cub.2003.12.034. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  34. ^ Labhart, Thomas (2009). "Specialized ommatidia of the polarization-sensitive dorsal rim area in the eye of monarch butterflies have non-functional reflecting tapeta". Cell Tissue Research. 338 (3): 391–400. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  35. ^ Heinze, S (2013). "Anatomical basis of sun compass navigation II: The neuronal composition of the central complex of the monarch butterfly". Comp Neurol. 521: 267-298. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  36. ^ Guerra, P (2012). "Discordant timing between antennae disrupts sun compass orientation in migratory monarch butterflies". Nat Commun. 3: 958. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  37. ^ Merlin, Christine (2009). "Antennal Circadian Clocks Coordinate Sun Compass Orientation in Migratory Monarch Butterflies". Science. 325 (1700–1704). doi:10.1126/science.1176221. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  38. ^ Merlin, Christine (2009). "Antennal Circadian Clocks Coordinate Sun Compass Orientation in Migratory Monarch Butterflies". Science. 325 (1700–1704). doi:10.1126/science.1176221. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  39. ^ Merlin, C (2012). "Discordant timing between antennae disrupts sun compass orientation in migratory monarch butterflies". Nat Commun. 3: 958. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  40. ^ Zhan S, Merlin C, Boore JL, Reppert SM (2011). "The Monarch Butterfly Genome Yields Insights into Long-Distance Migration". Cell. 147 (5): 1171–85. doi:10.1016/j.cell.2011.09.052. PMID 22118469. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  41. ^ Stensmyr MC, Hansson BS (2011). "A Genome Befitting a Monarch". Cell. 147 (5): 970–2. doi:10.1016/j.cell.2011.11.009. PMID 22118454. {{cite journal}}: Unknown parameter |month= ignored (help)
  42. ^ Johnson, Carolyn Y. (23 November 2011). "Monarch butterfly genome sequenced". The Boston Globe. Boston, MA. Retrieved 9 January 2012.
  43. ^ Zhan, S (9). "MonarchBase: the monarch butterfly genome database". Nucleic Acids Research Advance Access: 1–6. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  44. ^ Reppert, SM (2010). "Navigational mechanisms of migrating monarch butterflies". Trends in Neurosciences. 33: 391–434. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)

Template:Persondata

Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Steven_M._Reppert&oldid=552079870"