PITX2

PITX2
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	2L7F、2L7M、2LKX
識別號
别名	PITX2；, ARP1, Brx1, IDG2, IGDS, IGDS2, IHG2, IRID2, Otlx2, PTX2, RGS, RIEG, RIEG1, RS, paired like homeodomain 2, ASGD4
外部ID	OMIM：601542 MGI：109340 HomoloGene：55454 GeneCards：PITX2
相關疾病
	Axenfeld-Rieger syndrome type 1、虹膜發育不良綜合徵、ring dermoid of cornea、Rieger anomaly
基因位置（人类）
染色体	4號染色體
终止	110,642,123 bp
基因位置（小鼠）
染色体	小鼠3号染色体
终止	129,013,240 bp
RNA表达模式
	查阅更多表达数据
基因本體
分子功能	• 相同蛋白质结合; • protein homodimerization activity; • transcription cis-regulatory region binding; • sequence-specific DNA binding; • DNA结合; • 转录共激活因子活性; • chromatin DNA binding; • DNA-binding transcription activator activity, RNA polymerase II-specific; • 血浆蛋白结合; • RNA polymerase II cis-regulatory region sequence-specific DNA binding; • chromatin binding; • ribonucleoprotein complex binding; • DNA结合转录因子活性; • DNA结合转录阻遏物活性，RNA聚合酶II特异性; • 转录因子结合; • 磷蛋白结合; • DNA-binding transcription factor activity, RNA polymerase II-specific;
細胞組分	• 细胞核; • 細胞質; • 轉錄調節複合物; • 核质;
生物學過程	• response to vitamin A; • female gonad development; • vascular associated smooth muscle cell differentiation; • regulation of transcription by RNA polymerase II; • skeletal muscle tissue development; • cell proliferation involved in outflow tract morphogenesis; • prolactin secreting cell differentiation; • in utero embryonic development; • 垂体的发生; • 血管發生; • regulation of cell population proliferation; • myoblast fusion; • hair cell differentiation; • 脾的发生; • regulation of transcription, DNA-templated; • transcription by RNA polymerase II; • embryonic camera-type eye development; • ventricular septum morphogenesis; • endodermal digestive tract morphogenesis; • determination of left/right symmetry; • cardiac muscle tissue development; • positive regulation of transcription, DNA-templated; • subthalamic nucleus development; • ventricular cardiac muscle cell development; • left/right axis specification; • hypothalamus cell migration; • animal organ morphogenesis; • regulation of cell migration; • 心脏发育; • embryonic digestive tract morphogenesis; • branching involved in blood vessel morphogenesis; • cardiac muscle cell differentiation; • digestive system development; • multicellular organism development; • atrioventricular valve development; • pulmonary vein morphogenesis; • cardiac neural crest cell migration involved in outflow tract morphogenesis; • embryonic hindlimb morphogenesis; • lung development; • superior vena cava morphogenesis; • positive regulation of DNA binding; • extraocular skeletal muscle development; • pulmonary myocardium development; • deltoid tuberosity development; • atrial cardiac muscle tissue morphogenesis; • male gonad development; • anatomical structure morphogenesis; • brain development; • neuron differentiation; • odontogenesis of dentin-containing tooth; • Wnt信号通路; • left lung morphogenesis; • somatotropin secreting cell differentiation; • positive regulation of myoblast proliferation; • camera-type eye development; • response to hormone; • odontogenesis; • iris morphogenesis; • neuron migration; • negative regulation of transcription by RNA polymerase II; • positive regulation of transcription by RNA polymerase II;
	Sources:Amigo / QuickGO
直系同源
	5308
	18741
	ENSG00000164093
	ENSMUSG00000028023
	Q99697
	P97474
NM_000325; NM_001204397; NM_001204398; NM_001204399; NM_153426;
	NM_153427
	NM_001042502; NM_001042504; NM_001286942; NM_001287048; NM_011098
NP_000316; NP_001191326; NP_001191327; NP_001191328; NP_700475;
	NP_700476
	NP_001035967; NP_001035969; NP_001273871; NP_001273977; NP_035228
	維基數據
檢視/編輯人類	檢視/編輯小鼠

PITX2'（Paired-like homeodomain transcription factor 2（類成對同源框轉錄因子2）/pituitary homeobox 2（垂體同源框2））是一個位於人第四號染色體上的基因，由其編碼的蛋白為PITX2^[6]^[7]^[8]。

功能

PITX2蛋白屬於RIEG/PITX同源框蛋白家族，有一個屬於Bicoid（英语：Bicoid）蛋白家族的同源結構域。從功能上說，PITX2是一種轉錄因子^[9]，主要調控{{link-en|賴氨酰羥化酶|lysyl hydroxylase|前膠原賴氨酰羥化酶（procollagen lysyl hydroxylase）基因的表達。賴氨酰羥化酶參與眼、牙，以及腹部器官的發育過程。PITX2的轉錄調節火星受到催乳素的調節。已發現人體內的PITX2有三種轉錄變體^[8]。

PITX2在發育中與左—右軸的建立及左右不對稱性的形成有關，比如左側中胚層、心臟、肺、脾的不對稱發育及早起胃腸道的彎折。已證明在非人脊椎動物中，PITX2的同源基因亦有這樣的功能。敲除小鼠的Pitx2基因後，會導致身體左側器官形態發育異常。PITX2本身的表達受到ASE增強子和NODAL（英语：NODAL）蛋白的調控。目前的研究證據顯示NODAL蛋白主要調控頭部的PITX2基因表達，而ASE主要調控控制不對稱發展的PITX2基因的發展，如肝、脾的不對稱發展。在眼部發育中，PITX2能抑制眼外肌的自噬，並能控制其生長^[10]^[11]^[12]。PITX2的三種轉錄變體PITX2a、PITX2b、PITX2c各自都有不重疊的不同功能.^[13]。

PITX2亦參與了附肢形態形成。PITX2能調控MyoD基因的表達，使其在附肢形成過程中一直表達。MyoD基因與骨骼形態發生有關。研究表明Pixt2在肌肉中先於MyoD表達。要激活MyoD基因表達，PITX2首先會募集到MyoD的核心增強子上，然後激活MyoD的表達。Myf5、Myf6基因亦能調控MyoD的表達，但與PITX2之間互不影響。PITX2對附肢發育的調控依賴PAX3蛋白。在缺乏PAX3的情況下，即使PITX2表達附肢也無法形成。該實驗結果提示在調控通路中PITX2處於PAX3的下游，充當了PAX3和MyoD之間的中間體。總而言之，PITX2在附肢發育中是不可或缺的^[14]。

另外，有證據表明Pitx2在大鼠體內與性腺聲稱障礙有關^[15]。

已隱藏部分未翻譯内容，歡迎參與翻譯。

Clinical significance

Mutations in this gene are associated with Axenfeld-Rieger syndrome (ARS), iridogoniodysgenesis syndrome (IGDS), and sporadic cases of Peters anomaly. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes.^[8]

Pitx2 is overexpressed in many cancers. For example, thyroid,^[16] ovarian,^[17] and colon cancer^[18] all have higher levels of Pitx2 compared to noncancerous tissues. Scientists speculate that cancer cells improperly turn on Pitx2, leading to uncontrolled cell proliferation. This is consistent with the role of Pitx2 in regulating the growth-regulating genes cyclin D2,^[19] cyclin D1,^[20] and C-Myc.^[20]

In renal cancer, Pitx2 regulates expression of ABCB1, a multidrug transporter, by binding to the promoter region of ABCB1.^[21] Increased expression of Pitx2 in renal cancer cells is associated with increased expression of ABCB1.^[21] Thus, renal cancer cells that overexpress ABCB1 have a greater resistance to chemotherapeutic agents.^[21] In experiments where Pitx2 expression was decreased, renal cancer cells had decreased cell proliferation and greater susceptibility to doxorubicin treatment, which is consistent with other results.^[21]

In human esophageal squamous cell carcinoma (ESCC), Pitx2 is overexpressed compared to normal esophageal squamous cells.^[22] In addition, greater expression of Pitx2 is positively correlated with clinical aggressiveness of ESCC.^[22] Also, ESCC patients with high Pitx2 expression did not respond as well to definitive chemoradiotherapy (CRT) compared to ESCC patients with low Pitx2 expression.^[22] Thus, physicians may be able to use Pitx2 expression to predict how ESCC patients will respond to cancer treatment.^[22]

In Congenital Heart Disease, heterozygous mutations in Pitx2 have been involved in the development of Tetralogy of Fallot, ventricular septal defects, atrial septal defects, transposition of great arteries, and endocardial cushion defect (ECD).^[23]^[24]^[25] The mutations of the Pitx2 gene are created through alternative splicing. The isoform of Pitx2 important for cardiogenesis is Pitx2c. The lack of expression of this particular isoform correlates with these congenital defects. Pitx2 mutations significantly reduce transcriptional activity of Pitx2 and synergistic activation between Pitx2 and NKX2(also important for development of the heart).^[23] The large phenotypic spectrum due to the mutation of Pitx2 may be attributed to a variety of factors including: different genetic backgrounds, epigenetic modifiers and delayed/complete penetrance.^[24] It is important to note that the mutation of Pitx2 is not defined as the cause of these congenital heart defects, but currently perceived as a risk factor for their development.^[25]

參考

^ 與PITX2相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000164093 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000028023 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Arakawa H, Nakamura T, Zhadanov AB, Fidanza V, Yano T, Bullrich F, Shimizu M, Blechman J, Mazo A, Canaani E, Croce CM. Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene. Proceedings of the National Academy of Sciences of the United States of America. Apr 1998, 95 (8): 4573–8. PMC 22531 . PMID 9539779. doi:10.1073/pnas.95.8.4573.
^ Héon E, Sheth BP, Kalenak JW, Sunden SL, Streb LM, Taylor CM, Alward WL, Sheffield VC, Stone EM. Linkage of autosomal dominant iris hypoplasia to the region of the Rieger syndrome locus (4q25). Human Molecular Genetics. Aug 1995, 4 (8): 1435–9. PMID 7581385. doi:10.1093/hmg/4.8.1435.
^ ^8.0 ^8.1 ^8.2 Entrez Gene: PITX2 paired-like homeodomain transcription factor 2.
^ Logan M, Pagán-Westphal SM, Smith DM, Paganessi L, Tabin CJ. The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals. Cell. Aug 1998, 94 (3): 307–17. PMID 9708733. doi:10.1016/S0092-8674(00)81474-9.
^ Campione M, Steinbeisser H, Schweickert A, Deissler K, van Bebber F, Lowe LA, Nowotschin S, Viebahn C, Haffter P, Kuehn MR, Blum M. The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping. Development. Mar 1999, 126 (6): 1225–34. PMID 10021341.
^ Shiratori H, Yashiro K, Shen MM, Hamada H. Conserved regulation and role of Pitx2 in situs-specific morphogenesis of visceral organs. Development. Aug 2006, 133 (15): 3015–25. PMID 16835440. doi:10.1242/dev.02470.
^ Zacharias AL, Lewandoski M, Rudnicki MA, Gage PJ. Pitx2 is an upstream activator of extraocular myogenesis and survival. Developmental Biology. Jan 2011, 349 (2): 395–405. PMC 3019256 . PMID 21035439. doi:10.1016/j.ydbio.2010.10.028.
^ Essner JJ, Branford WW, Zhang J, Yost HJ. Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms. Development. Mar 2000, 127 (5): 1081–93. PMID 10662647.
^ L'honoré A, Ouimette JF, Lavertu-Jolin M, Drouin J. Pitx2 defines alternate pathways acting through MyoD during limb and somitic myogenesis. Development. Nov 2010, 137 (22): 3847–56. PMID 20978076. doi:10.1242/dev.053421.
^ Nandi SS, Ghosh P, Roy SS. Expression of PITX2 homeodomain transcription factor during rat gonadal development in a sexually dimorphic manner. Cellular Physiology and Biochemistry. 2011, 27 (2): 159–70. PMID 21325833. doi:10.1159/000325218.
^ Huang Y, Guigon CJ, Fan J, Cheng SY, Zhu GZ. Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2. Cell Cycle. Apr 2010, 9 (7): 1333–41. PMID 20372070. doi:10.4161/cc.9.7.11126.
^ Fung FK, Chan DW, Liu VW, Leung TH, Cheung AN, Ngan HY. Increased expression of PITX2 transcription factor contributes to ovarian cancer progression. PLOS ONE. 2012, 7 (5): e37076. PMC 3352869 . PMID 22615897. doi:10.1371/journal.pone.0037076.
^ Hirose H, Ishii H, Mimori K, Tanaka F, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M. The significance of PITX2 overexpression in human colorectal cancer. Annals of Surgical Oncology. Oct 2011, 18 (10): 3005–12. PMID 21479692. doi:10.1245/s10434-011-1653-z.
^ Kioussi C, Briata P, Baek SH, Rose DW, Hamblet NS, Herman T, Ohgi KA, Lin C, Gleiberman A, Wang J, Brault V, Ruiz-Lozano P, Nguyen HD, Kemler R, Glass CK, Wynshaw-Boris A, Rosenfeld MG. Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development. Cell. Nov 2002, 111 (5): 673–85. PMID 12464179. doi:10.1016/s0092-8674(02)01084-x.
^ ^20.0 ^20.1 Baek SH, Kioussi C, Briata P, Wang D, Nguyen HD, Ohgi KA, Glass CK, Wynshaw-Boris A, Rose DW, Rosenfeld MG. Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway. Proceedings of the National Academy of Sciences of the United States of America. Mar 2003, 100 (6): 3245–3250. PMC 152277 . PMID 12629224. doi:10.1073/pnas.0330217100.
^ ^21.0 ^21.1 ^21.2 ^21.3 Lee WK, Chakraborty PK, Thévenod F. Pituitary homeobox 2 (PITX2) protects renal cancer cell lines against doxorubicin toxicity by transcriptional activation of the multidrug transporter ABCB1. International Journal of Cancer. Journal International Du Cancer. Aug 2013, 133 (3): 556–67. PMID 23354914. doi:10.1002/ijc.28060.
^ ^22.0 ^22.1 ^22.2 ^22.3 Zhang JX, Tong ZT, Yang L, Wang F, Chai HP, Zhang F, Xie MR, Zhang AL, Wu LM, Hong H, Yin L, Wang H, Wang HY, Zhao Y. PITX2: a promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma. International Journal of Cancer. Journal International Du Cancer. Jun 2013, 132 (11): 2567–2577. PMID 23132660. doi:10.1002/ijc.27930.
^ ^23.0 ^23.1 Sun, Y. PITX2 loss-of-function mutation contributes to tetralogy of Fallot. Gene. February 15, 2016, 577: 258–264. PMID 26657035. doi:10.1016/j.gene.2015.12.001.
^ ^24.0 ^24.1 Zhao, C. PITX2 Loss-of-Function Mutation contributes to Congenital Endocardial Cushion Defect and Axenfold-Rieger Syndrome. PLOS ONE. April 20, 2015, 10: e0124409. PMC 4404345 . PMID 25893250. doi:10.1371/journal.pone.0124409.
^ ^25.0 ^25.1 Dong, Wei. Novel Pitx2c loss-of-function mutations associated with complex congenital heart disease. International Journal of Molecular Medicine. January 14, 2014. doi:10.3892/ijmm.2014.168.

拓展閱讀

Franco D, Campione M. The role of Pitx2 during cardiac development. Linking left-right signaling and congenital heart diseases. Trends in Cardiovascular Medicine. May 2003, 13 (4): 157–63. PMID 12732450. doi:10.1016/S1050-1738(03)00039-2.
Hjalt TA, Semina EV. Current molecular understanding of Axenfeld-Rieger syndrome. Expert Reviews in Molecular Medicine. Nov 2005, 7 (25): 1–17. PMID 16274491. doi:10.1017/S1462399405010082.
Murray JC, Bennett SR, Kwitek AE, Small KW, Schinzel A, Alward WL, Weber JL, Bell GI, Buetow KH. Linkage of Rieger syndrome to the region of the epidermal growth factor gene on chromosome 4. Nature Genetics. Sep 1992, 2 (1): 46–9. PMID 1303248. doi:10.1038/ng0992-46.
Walter MA, Mirzayans F, Mears AJ, Hickey K, Pearce WG. Autosomal-dominant iridogoniodysgenesis and Axenfeld-Rieger syndrome are genetically distinct. Ophthalmology. Nov 1996, 103 (11): 1907–15. PMID 8942889. doi:10.1016/s0161-6420(96)30408-9.
Semina EV, Reiter R, Leysens NJ, Alward WL, Small KW, Datson NA, Siegel-Bartelt J, Bierke-Nelson D, Bitoun P, Zabel BU, Carey JC, Murray JC. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nature Genetics. Dec 1996, 14 (4): 392–9. PMID 8944018. doi:10.1038/ng1296-392.
Alward WL, Semina EV, Kalenak JW, Héon E, Sheth BP, Stone EM, Murray JC. Autosomal dominant iris hypoplasia is caused by a mutation in the Rieger syndrome (RIEG/PITX2) gene. American Journal of Ophthalmology. Jan 1998, 125 (1): 98–100. PMID 9437321. doi:10.1016/S0002-9394(99)80242-6.
Kulak SC, Kozlowski K, Semina EV, Pearce WG, Walter MA. Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome. Human Molecular Genetics. Jul 1998, 7 (7): 1113–7. PMID 9618168. doi:10.1093/hmg/7.7.1113.
Amendt BA, Sutherland LB, Semina EV, Russo AF. The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities. The Journal of Biological Chemistry. Aug 1998, 273 (32): 20066–72. PMID 9685346. doi:10.1074/jbc.273.32.20066.
Yoshioka H, Meno C, Koshiba K, Sugihara M, Itoh H, Ishimaru Y, Inoue T, Ohuchi H, Semina EV, Murray JC, Hamada H, Noji S. Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry. Cell. Aug 1998, 94 (3): 299–305. PMID 9708732. doi:10.1016/S0092-8674(00)81473-7.
Doward W, Perveen R, Lloyd IC, Ridgway AE, Wilson L, Black GC. A mutation in the RIEG1 gene associated with Peters' anomaly. Journal of Medical Genetics. Feb 1999, 36 (2): 152–5. PMC 1734311 . PMID 10051017. doi:10.1136/jmg.36.2.152.
Pellegrini-Bouiller I, Manrique C, Gunz G, Grino M, Zamora AJ, Figarella-Branger D, Grisoli F, Jaquet P, Enjalbert A. Expression of the members of the Ptx family of transcription factors in human pituitary adenomas. The Journal of Clinical Endocrinology and Metabolism. Jun 1999, 84 (6): 2212–20. PMID 10372733. doi:10.1210/jc.84.6.2212.
Hjalt TA, Amendt BA, Murray JC. PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression: implications for the pathology of Rieger syndrome. The Journal of Cell Biology. Feb 2001, 152 (3): 545–52. PMC 2196000 . PMID 11157981. doi:10.1083/jcb.152.3.545.
Priston M, Kozlowski K, Gill D, Letwin K, Buys Y, Levin AV, Walter MA, Héon E. Functional analyses of two newly identified PITX2 mutants reveal a novel molecular mechanism for Axenfeld-Rieger syndrome. Human Molecular Genetics. Aug 2001, 10 (16): 1631–8. PMID 11487566. doi:10.1093/hmg/10.16.1631.
Green PD, Hjalt TA, Kirk DE, Sutherland LB, Thomas BL, Sharpe PT, Snead ML, Murray JC, Russo AF, Amendt BA. Antagonistic regulation of Dlx2 expression by PITX2 and Msx2: implications for tooth development. Gene Expression. 2002, 9 (6): 265–81. PMID 11763998.
Vincent AL, Billingsley G, Buys Y, Levin AV, Priston M, Trope G, Williams-Lyn D, Héon E. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. American Journal of Human Genetics. Feb 2002, 70 (2): 448–60. PMC 384919 . PMID 11774072. doi:10.1086/338709.
Borges AS, Susanna R, Carani JC, Betinjane AJ, Alward WL, Stone EM, Sheffield VC, Nishimura DY. Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil. Journal of Glaucoma. Feb 2002, 11 (1): 51–6. PMID 11821690. doi:10.1097/00061198-200202000-00010.
Cox CJ, Espinoza HM, McWilliams B, Chappell K, Morton L, Hjalt TA, Semina EV, Amendt BA. Differential regulation of gene expression by PITX2 isoforms. The Journal of Biological Chemistry. Jul 2002, 277 (28): 25001–10. PMID 11948188. doi:10.1074/jbc.M201737200.
Quentien MH, Pitoia F, Gunz G, Guillet MP, Enjalbert A, Pellegrini I. Regulation of prolactin, GH, and Pit-1 gene expression in anterior pituitary by Pitx2: An approach using Pitx2 mutants. Endocrinology. Aug 2002, 143 (8): 2839–51. PMID 12130547. doi:10.1210/en.143.8.2839.

外部連結

醫學主題詞表（MeSH）：PITX2+protein,+human

PITX2引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。

[1] 與PITX2相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000164093 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000028023 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9539779-6] Arakawa H, Nakamura T, Zhadanov AB, Fidanza V, Yano T, Bullrich F, Shimizu M, Blechman J, Mazo A, Canaani E, Croce CM. Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene. Proceedings of the National Academy of Sciences of the United States of America. Apr 1998, 95 (8): 4573–8. PMC 22531 . PMID 9539779. doi:10.1073/pnas.95.8.4573.

[pmid7581385-7] Héon E, Sheth BP, Kalenak JW, Sunden SL, Streb LM, Taylor CM, Alward WL, Sheffield VC, Stone EM. Linkage of autosomal dominant iris hypoplasia to the region of the Rieger syndrome locus (4q25). Human Molecular Genetics. Aug 1995, 4 (8): 1435–9. PMID 7581385. doi:10.1093/hmg/4.8.1435.

[entrez-8] 8.0 ^8.1 ^8.2 Entrez Gene: PITX2 paired-like homeodomain transcription factor 2.

[tabin-9] Logan M, Pagán-Westphal SM, Smith DM, Paganessi L, Tabin CJ. The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals. Cell. Aug 1998, 94 (3): 307–17. PMID 9708733. doi:10.1016/S0092-8674(00)81474-9.

[pmid10021341-10] Campione M, Steinbeisser H, Schweickert A, Deissler K, van Bebber F, Lowe LA, Nowotschin S, Viebahn C, Haffter P, Kuehn MR, Blum M. The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping. Development. Mar 1999, 126 (6): 1225–34. PMID 10021341.

[pmid16835440-11] Shiratori H, Yashiro K, Shen MM, Hamada H. Conserved regulation and role of Pitx2 in situs-specific morphogenesis of visceral organs. Development. Aug 2006, 133 (15): 3015–25. PMID 16835440. doi:10.1242/dev.02470.

[pmid21035439-12] Zacharias AL, Lewandoski M, Rudnicki MA, Gage PJ. Pitx2 is an upstream activator of extraocular myogenesis and survival. Developmental Biology. Jan 2011, 349 (2): 395–405. PMC 3019256 . PMID 21035439. doi:10.1016/j.ydbio.2010.10.028.

[pmid10662647-13] Essner JJ, Branford WW, Zhang J, Yost HJ. Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms. Development. Mar 2000, 127 (5): 1081–93. PMID 10662647.

[Pitx2_and_Myogenesis-14] L'honoré A, Ouimette JF, Lavertu-Jolin M, Drouin J. Pitx2 defines alternate pathways acting through MyoD during limb and somitic myogenesis. Development. Nov 2010, 137 (22): 3847–56. PMID 20978076. doi:10.1242/dev.053421.

[pmid21325833-15] Nandi SS, Ghosh P, Roy SS. Expression of PITX2 homeodomain transcription factor during rat gonadal development in a sexually dimorphic manner. Cellular Physiology and Biochemistry. 2011, 27 (2): 159–70. PMID 21325833. doi:10.1159/000325218.

[pmid20372070-16] Huang Y, Guigon CJ, Fan J, Cheng SY, Zhu GZ. Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2. Cell Cycle. Apr 2010, 9 (7): 1333–41. PMID 20372070. doi:10.4161/cc.9.7.11126.

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