Gene Symbol: Pitx2
Description: paired-like homeodomain transcription factor 2
Alias: 9430085M16Rik, Brx1, Brx1b, Munc30, Otlx2, Ptx2, Rieg, pituitary homeobox 2, ALL1-responsive protein ARP1, BRX1 homeoprotein, orthodenticle-like homeobox 2, paired-like homeodomain transcription factor Munc 30, solurshin
Species: mouse
Products:     Pitx2

Top Publications

  1. Muccielli M, Martinez S, Pattyn A, Goridis C, Brunet J. Otlx2, an Otx-related homeobox gene expressed in the pituitary gland and in a restricted pattern in the forebrain. Mol Cell Neurosci. 1996;8:258-71 pubmed
    ..Here, we report on the isolation of a new homeobox gene of the paired superclass, Otlx2, whose early expression pattern in the mesencephalon and prosencephalon is congruent with proposed neuromeric ..
  2. Wang X, O Connell D, Lund J, Saadi I, Kuraguchi M, Turbe Doan A, et al. Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood. Development. 2009;136:1939-49 pubmed publisher
    ..In addition, we identify Fgf8, a known tooth initiation marker, as a direct target of Wnt/beta-catenin signaling. These studies identify key mechanistic features responsible for supernumerary tooth formation. ..
  3. Vermot J, Gallego Llamas J, Fraulob V, Niederreither K, Chambon P, Dolle P. Retinoic acid controls the bilateral symmetry of somite formation in the mouse embryo. Science. 2005;308:563-6 pubmed
    ..These data implicate retinoic acid as an endogenous signal that maintains the bilateral synchrony of mesoderm segmentation, and therefore controls bilateral symmetry, in vertebrate embryos. ..
  4. Hilton T, Gross M, Kioussi C. Pitx2-dependent occupancy by histone deacetylases is associated with T-box gene regulation in mammalian abdominal tissue. J Biol Chem. 2010;285:11129-42 pubmed publisher
    The homeodomain transcription factor Pitx2 and the T-box transcription factors are essential for organogenesis. Pitx2 and T-box genes are induced by growth factors and function as transcriptional activators or repressors...
  5. Marques S, Borges A, Silva A, Freitas S, Cordenonsi M, Belo J. The activity of the Nodal antagonist Cerl-2 in the mouse node is required for correct L/R body axis. Genes Dev. 2004;18:2342-7 pubmed
    ..Our results demonstrate that Cerl-2 plays a key role in restricting the Nodal signaling pathway toward the left side of the mouse embryo by preventing its activity in the right side. ..
  6. Chen Y, Ishii M, Sun J, Sucov H, Maxson R. Msx1 and Msx2 regulate survival of secondary heart field precursors and post-migratory proliferation of cardiac neural crest in the outflow tract. Dev Biol. 2007;308:421-37 pubmed
  7. Matt N, Ghyselinck N, Pellerin I, Dupé V. Impairing retinoic acid signalling in the neural crest cells is sufficient to alter entire eye morphogenesis. Dev Biol. 2008;320:140-8 pubmed publisher
    ..Furthermore, we point out that Pitx2, which encodes a homeodomain transcription factor, is a key RA-responsive gene in neural crest cells during eye ..
  8. Amen M, Liu X, Vadlamudi U, Elizondo G, Diamond E, Engelhardt J, et al. PITX2 and beta-catenin interactions regulate Lef-1 isoform expression. Mol Cell Biol. 2007;27:7560-73 pubmed
    Lef-1 and PITX2 function in the Wnt signaling pathway by recruiting and interacting with beta-catenin to activate target genes. Chromatin immunoprecipitation (ChIP) assays identified the Lef-1 promoter as a PITX2 downstream target...
  9. Charles M, Suh H, Hjalt T, Drouin J, Camper S, Gage P. PITX genes are required for cell survival and Lhx3 activation. Mol Endocrinol. 2005;19:1893-903 pubmed
    ..Pitx1 mutants have a mild pituitary phenotype, but Pitx2 is necessary for the development of Rathke's pouch, expression of essential transcription factors in gonadotropes, ..

More Information


  1. Tessari A, Pietrobon M, Notte A, Cifelli G, Gage P, Schneider M, et al. Myocardial Pitx2 differentially regulates the left atrial identity and ventricular asymmetric remodeling programs. Circ Res. 2008;102:813-22 pubmed publisher
    The Pitx2 gene regulates left-right (L/R) asymmetrical cardiac morphogenesis...
  2. Zhou W, Lin L, Majumdar A, Li X, Zhang X, Liu W, et al. Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2. Nat Genet. 2007;39:1225-34 pubmed
    ..Thus, we propose that transcriptional readout mediated at least in part by a Wnt11 --> ATF/CREB --> TGFbeta2 pathway is critical in regulating morphogenesis in response to noncanonical Wnt signaling. ..
  3. Saijoh Y, Oki S, Ohishi S, Hamada H. Left-right patterning of the mouse lateral plate requires nodal produced in the node. Dev Biol. 2003;256:160-72 pubmed
    ..These results indicate that Nodal produced in the node is required for expression of Nodal and other left side-specific genes in the LPM. ..
  4. Purandare S, Ware S, Kwan K, Gebbia M, Bassi M, Deng J, et al. A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice. Development. 2002;129:2293-302 pubmed
    ..Subsequent nodal and Pitx2 expression in the lateral plate mesoderm in these mice is randomized, indicating that Zic3 acts upstream of these ..
  5. Ammirabile G, Tessari A, Pignataro V, Szumska D, Sutera Sardo F, Benes J, et al. Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium. Cardiovasc Res. 2012;93:291-301 pubmed publisher
    ..The role of the laterality gene Pitx2 in this process is unknown...
  6. Sambasivan R, Gayraud Morel B, Dumas G, Cimper C, Paisant S, Kelly R, et al. Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates. Dev Cell. 2009;16:810-21 pubmed publisher
    ..These findings identify novel genetic networks that may provide insights into myopathies which often affect only subsets of muscles...
  7. Krebs L, Iwai N, Nonaka S, Welsh I, Lan Y, Jiang R, et al. Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev. 2003;17:1207-12 pubmed
    ..Our results demonstrate that Dll1-mediated Notch signaling is essential for generation of left-right asymmetry, and that the Notch pathway acts upstream of Nodal expression during left-right asymmetry determination in mice. ..
  8. Gage P, Suh H, Camper S. The bicoid-related Pitx gene family in development. Mamm Genome. 1999;10:197-200 pubmed
  9. Semina E, Reiter R, Leysens N, Alward W, Small K, Datson N, et al. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet. 1996;14:392-9 pubmed
    Rieger syndrome (RIEG) is an autosomal-dominant human disorder that includes anomalies of the anterior chamber of the eye, dental hypoplasia and a protuberant umbilicus...
  10. Zacharias A, Lewandoski M, Rudnicki M, Gage P. Pitx2 is an upstream activator of extraocular myogenesis and survival. Dev Biol. 2011;349:395-405 pubmed publisher
    ..We show Pax7 is dispensable for extraocular muscle formation, whereas Pitx2 is cell-autonomously required to prevent apoptosis of the extraocular muscle primordia...
  11. Swindell E, Liu C, Shah R, Smith A, Lang R, Jamrich M. Eye formation in the absence of retina. Dev Biol. 2008;322:56-64 pubmed publisher
    ..One involved in the formation of the eyeball and the second involved in the formation of the auxiliary eye structures. ..
  12. Ryan A, Blumberg B, Rodriguez Esteban C, Yonei Tamura S, Tamura K, Tsukui T, et al. Pitx2 determines left-right asymmetry of internal organs in vertebrates. Nature. 1998;394:545-51 pubmed
    ..The gene Pitx2 is expressed in the left lateral plate mesoderm and, subsequently, in the left heart and gut of mouse, chick and ..
  13. Murray S, Gridley T. Snail family genes are required for left-right asymmetry determination, but not neural crest formation, in mice. Proc Natl Acad Sci U S A. 2006;103:10300-10304 pubmed publisher
  14. Lopes Floro K, Artap S, Preis J, Fatkin D, Chapman G, Furtado M, et al. Loss of Cited2 causes congenital heart disease by perturbing left-right patterning of the body axis. Hum Mol Genet. 2011;20:1097-110 pubmed publisher
    ..The clinical relevance of these findings lies in the fact that heterozygous mutation of human CITED2 is associated with congenital heart disease and laterality defects. ..
  15. Gage P, Qian M, Wu D, Rosenberg K. The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development. Dev Biol. 2008;317:310-24 pubmed publisher
    ..we show that Dkk2, encoding an antagonist of canonical Wnt signaling, is an essential downstream target of the PITX2 homeodomain transcription factor in neural crest during eye development...
  16. Lu M, Pressman C, Dyer R, Johnson R, Martin J. Function of Rieger syndrome gene in left-right asymmetry and craniofacial development. Nature. 1999;401:276-8 pubmed
    Rieger syndrome, an autosomal dominant disorder, includes ocular, craniofacial and umbilical abnormalities. The pitx2 homeobox gene, which is mutated in Rieger syndrome, has been proposed to be the effector molecule interpreting left-..
  17. Hjalt T, Amendt B, Murray J. PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression: implications for the pathology of Rieger syndrome. J Cell Biol. 2001;152:545-52 pubmed
    ..Patients have mutations in PITX2, a paired-bicoid homeobox gene, also involved in left/right polarity determination...
  18. Meyers E, Martin G. Differences in left-right axis pathways in mouse and chick: functions of FGF8 and SHH. Science. 1999;285:403-6 pubmed
    ..In the mouse FGF8 is a left determinant and Sonic Hedgehog is required to prevent left determinants from being expressed on the right. ..
  19. McGrath J, Somlo S, Makova S, Tian X, Brueckner M. Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell. 2003;114:61-73 pubmed
  20. Liu W, Selever J, Wang D, Lu M, Moses K, Schwartz R, et al. Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. Proc Natl Acad Sci U S A. 2004;101:4489-94 pubmed
    ..Our findings uncover a previously uncharacterized function for Bmp4 in vascular remodeling of the BAAs, and they show definitively that Bmp4, in cooperation with Bmp7, has a central role in OFT septation. ..
  21. Raya A, Kawakami Y, Rodriguez Esteban C, Buscher D, Koth C, Itoh T, et al. Notch activity induces Nodal expression and mediates the establishment of left-right asymmetry in vertebrate embryos. Genes Dev. 2003;17:1213-8 pubmed
    ..Our findings provide evidence for a mechanism involving Notch activity that translates an initial symmetry-breaking event into asymmetric gene expression. ..
  22. Ai D, Liu W, Ma L, Dong F, Lu M, Wang D, et al. Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium. Dev Biol. 2006;296:437-49 pubmed
    ..The Pitx2 homeobox gene functions at the final stages of this cascade to direct asymmetric morphogenesis of selected organs ..
  23. Logan M, Pagán Westphal S, Smith D, Paganessi L, Tabin C. The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals. Cell. 1998;94:307-17 pubmed
    The mechanism by which asymmetric signals induce left-right-specific morphogenesis has been elusive. Pitx2 encodes a transcription factor expressed throughout the left lateral plate mesoderm and subsequently on the left side of ..
  24. Tsukui T, Capdevila J, Tamura K, Ruiz Lozano P, Rodriguez Esteban C, Yonei Tamura S, et al. Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1. Proc Natl Acad Sci U S A. 1999;96:11376-81 pubmed
    ..Thus, the roles of Shh and RA in left-right specification indeed are conserved among vertebrates, and the Shh and RA pathways converge in the control of Lefty-1. ..
  25. Ganga M, Espinoza H, Cox C, Morton L, Hjalt T, Lee Y, et al. PITX2 isoform-specific regulation of atrial natriuretic factor expression: synergism and repression with Nkx2.5. J Biol Chem. 2003;278:22437-45 pubmed
    b>PITX2 and Nkx2.5 are two of the earliest known transcriptional markers of vertebrate heart development. Pitx2-/- mice present with severe cardiac malformations and embryonic lethality, demonstrating a role for PITX2 in heart development...
  26. Nakaya M, Biris K, Tsukiyama T, Jaime S, Rawls J, Yamaguchi T. Wnt3a links left-right determination with segmentation and anteroposterior axis elongation. Development. 2005;132:5425-36 pubmed
    ..Thus, Wnt3a links the segmentation clock and AP axis elongation with key left-determining events, suggesting that Wnt3a is an integral component of the trunk organizer. ..
  27. Marszalek J, Ruiz Lozano P, Roberts E, Chien K, Goldstein L. Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. Proc Natl Acad Sci U S A. 1999;96:5043-8 pubmed
  28. Brennan J, Norris D, Robertson E. Nodal activity in the node governs left-right asymmetry. Genes Dev. 2002;16:2339-44 pubmed
    ..Our findings confirm that the mouse node is instrumental in initiating left-right axis specification and identify Nodal as the key morphogen regulating this process. ..
  29. Espinoza H, Ganga M, Vadlamudi U, Martin D, Brooks B, Semina E, et al. Protein kinase C phosphorylation modulates N- and C-terminal regulatory activities of the PITX2 homeodomain protein. Biochemistry. 2005;44:3942-54 pubmed
    PKC phosphorylation regulates PITX2 DNA binding and transcriptional activity. Mutation of individual PKC sites demonstrates the functional regulation of PITX2 through phosphorylation...
  30. Houde C, Dickinson R, Houtzager V, Cullum R, Montpetit R, Metzler M, et al. Hippi is essential for node cilia assembly and Sonic hedgehog signaling. Dev Biol. 2006;300:523-33 pubmed
  31. Wang J, Klysik E, Sood S, Johnson R, Wehrens X, Martin J. Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification. Proc Natl Acad Sci U S A. 2010;107:9753-8 pubmed publisher
    ..studies implicated a region of human chromosome 4q25 in familial AF and AFL, approximately 150 kb distal to the Pitx2 homeobox gene, a developmental left-right asymmetry (LRA) gene...
  32. Gage P, Camper S. Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation. Hum Mol Genet. 1997;6:457-64 pubmed
    ..The proteins have been named Ptx2a and Ptx2b since they are highly related to Ptx1/P-OTX. Ptx2 is expressed in both developing and adult pituitary gland, eye and brain tissues, suggesting an important role in ..
  33. Shih H, Gross M, Kioussi C. Cranial muscle defects of Pitx2 mutants result from specification defects in the first branchial arch. Proc Natl Acad Sci U S A. 2007;104:5907-12 pubmed
    b>Pitx2 expression is observed during all states of the myogenic progression in embryonic muscle anlagen and persists in adult muscle. Pitx2 mutant mice form all but a few muscle anlagen...
  34. Evans A, Gage P. Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development. Hum Mol Genet. 2005;14:3347-59 pubmed
    Heterozygous mutations in the homeobox gene, PITX2, result in ocular anterior segment defects and a high incidence of early-onset glaucoma...
  35. Maisonneuve C, Guilleret I, Vick P, Weber T, Andre P, Beyer T, et al. Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow. Development. 2009;136:3019-30 pubmed publisher
    ..These results suggest a model whereby BicC links the orientation of cilia with PCP, possibly by regulating RNA silencing in P-bodies. ..
  36. Schweickert A, Campione1 M, Steinbeisser H, Blum M. Pitx2 isoforms: involvement of Pitx2c but not Pitx2a or Pitx2b in vertebrate left-right asymmetry. Mech Dev. 2000;90:41-51 pubmed
    During vertebrate left-right development the homeobox gene Pitx2 serves as a mediator between transient nodal signaling in the left lateral plate mesoderm (l-LPM) and asymmetric organ morphogenesis...
  37. Weninger W, Lopes Floro K, Bennett M, Withington S, Preis J, Barbera J, et al. Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development. Development. 2005;132:1337-48 pubmed
    ..We show by gene expression analysis that Cited2 acts upstream of Nodal, Lefty2 and Pitx2 in the lateral mesoderm, and of Lefty1 in the presumptive floor plate...
  38. Bamforth S, Braganca J, Farthing C, Schneider J, Broadbent C, Michell A, et al. Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway. Nat Genet. 2004;36:1189-96 pubmed
    ..We propose that an abnormal Nodal-Pitx2c pathway represents a unifying mechanism for the cardiovascular malformations observed in Cited2(-/-) mice, and that such malformations may be the sole manifestation of a laterality defect. ..
  39. Mommersteeg M, Hoogaars W, Prall O, de Gier de Vries C, Wiese C, Clout D, et al. Molecular pathway for the localized formation of the sinoatrial node. Circ Res. 2007;100:354-62 pubmed
  40. Matt N, Dupé V, Garnier J, Dennefeld C, Chambon P, Mark M, et al. Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells. Development. 2005;132:4789-800 pubmed
    ..1) the remodeling of the POM through activation of Eya2-related apoptosis; (2) the expression of Foxc1 and Pitx2, which play crucial roles in anterior eye segment development; and (3) the growth of the ventral retina...
  41. Lin C, Kioussi C, O Connell S, Briata P, Szeto D, Liu F, et al. Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis. Nature. 1999;401:279-82 pubmed
    Pitx1 and Pitx2 are highly homologous, bicoid-related transcription factors. Pitx2 was initially identified as the gene responsible for the human Rieger syndrome, an autosomal dominant condition that causes developmental abnormalities...
  42. Yan Y, Gritsman K, Ding J, Burdine R, Corrales J, Price S, et al. Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation. Genes Dev. 1999;13:2527-37 pubmed
    ..In both Cryptic and oep mutant embryos, L-R asymmetric expression of Nodal/cyclops, Lefty2/antivin, and Pitx2 does not occur in the lateral plate mesoderm, while in Cryptic mutants Lefty1 expression is absent from the ..
  43. Gaussin V, Van de Putte T, Mishina Y, Hanks M, Zwijsen A, Huylebroeck D, et al. Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3. Proc Natl Acad Sci U S A. 2002;99:2878-83 pubmed
    ..Hence, ALK3 is essential, beyond just the egg cylinder stage, for myocyte-dependent functions and signals in cardiac organogenesis. ..
  44. Kitamura K, Miura H, Yanazawa M, Miyashita T, Kato K. Expression patterns of Brx1 (Rieg gene), Sonic hedgehog, Nkx2.2, Dlx1 and Arx during zona limitans intrathalamica and embryonic ventral lateral geniculate nuclear formation. Mech Dev. 1997;67:83-96 pubmed
    ..Brx1 is a member of the Brx gene family and comprises the genes for Brx1a and Brx1b, which differ in the sequence in the region located on the 5'-terminal side of the homeobox...
  45. Arakawa H, Nakamura T, Zhadanov A, Fidanza V, Yano T, Bullrich F, et al. Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene. Proc Natl Acad Sci U S A. 1998;95:4573-8 pubmed
    ..The gene, designated ARP1 (also termed RIEG, Ptx2, or Otlx2), is a member of a family of homeotic genes containing a short motif shared with several homeobox genes...
  46. Suh H, Gage P, Drouin J, Camper S. Pitx2 is required at multiple stages of pituitary organogenesis: pituitary primordium formation and cell specification. Development. 2002;129:329-37 pubmed
    Analysis of an allelic series in mice revealed that the Pitx2 homeobox gene is required at multiple stages of pituitary development...
  47. Cao H, Wang J, Li X, Florez S, Huang Z, Venugopalan S, et al. MicroRNAs play a critical role in tooth development. J Dent Res. 2010;89:779-84 pubmed publisher
    ..Conditional knockout (cKO) of Dicer1 (mature microRNAs) in the dental epithelium of the Pitx2-Cre mouse results in multiple and branched enamel-free incisors and cuspless molars, and change in incisor ..
  48. L honoré A, Coulon V, Marcil A, Lebel M, Lafrance Vanasse J, Gage P, et al. Sequential expression and redundancy of Pitx2 and Pitx3 genes during muscle development. Dev Biol. 2007;307:421-33 pubmed
    ..We now report the expression of Pitx2 and Pitx3 transcription factors throughout muscle development...
  49. Lamba P, Khivansara V, D Alessio A, Santos M, Bernard D. Paired-like homeodomain transcription factors 1 and 2 regulate follicle-stimulating hormone beta-subunit transcription through a conserved cis-element. Endocrinology. 2008;149:3095-108 pubmed publisher
    ..We observed that endogenous PITX1 and PITX2 isoforms from murine LbetaT2 gonadotrope cells could bind a highly conserved proximal cis-element...
  50. Liu C, Liu W, Lu M, Brown N, Martin J. Regulation of left-right asymmetry by thresholds of Pitx2c activity. Development. 2001;128:2039-48 pubmed
    ..The Pitx2 homeobox gene plays an important role in the final stages of asymmetry...
  51. Chen J, Lan Y, Baek J, Gao Y, Jiang R. Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev Biol. 2009;334:174-85 pubmed publisher
    ..Together, these results indicate that activation of the mesenchymal odontogenic program during early tooth development requires concerted actions of Bmp, Fgf and Wnt signaling from the presumptive dental epithelium to the mesenchyme...
  52. Vadlamudi U, Espinoza H, Ganga M, Martin D, Liu X, Engelhardt J, et al. PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter. J Cell Sci. 2005;118:1129-37 pubmed
    b>PITX2, beta-catenin and lymphoid enhancer factor (LEF-1) are required for the inductive formation of several epithelial-derived organs, including teeth...
  53. Hjalt T, Semina E, Amendt B, Murray J. The Pitx2 protein in mouse development. Dev Dyn. 2000;218:195-200 pubmed
    ..syndrome, an autosomal dominant disorder involving ocular, dental, and umbilical defects is caused by mutations in PITX2, a Bicoid-type homeobox protein...
  54. Meno C, Shimono A, Saijoh Y, Yashiro K, Mochida K, Ohishi S, et al. lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. Cell. 1998;94:287-97 pubmed
    ..The lack of lefty-1 resulted in bilateral expression of nodal, lefty-2, and Pitx2 (a homeobox gene normally expressed on the left side)...
  55. Yoshioka H, Meno C, Koshiba K, Sugihara M, Itoh H, Ishimaru Y, et al. Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry. Cell. 1998;94:299-305 pubmed
    ..However, a common signaling pathway has not yet been identified in vertebrates. We report that Pitx2, a bicoid-type homeobox gene expressed asymmetrically in the left lateral plate mesoderm, may be involved in ..
  56. Takeuchi J, Mileikovskaia M, Koshiba Takeuchi K, Heidt A, Mori A, Arruda E, et al. Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development. Development. 2005;132:2463-74 pubmed
    ..We conclude that Tbx20 is positioned at a critical node in transcription factor networks required for heart and motoneuron development where it dose-dependently regulates gene expression. ..
  57. Hamblet N, Lijam N, Ruiz Lozano P, Wang J, Yang Y, Luo Z, et al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure. Development. 2002;129:5827-38 pubmed
    ..Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during ..
  58. Hoodless P, Pye M, Chazaud C, Labbe E, Attisano L, Rossant J, et al. FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse. Genes Dev. 2001;15:1257-71 pubmed
    ..These results show that FoxH1 functions in an activin/nodal-Smad signaling pathway that acts upstream of Foxa2 and is required specifically for patterning the APS and node in the mouse. ..
  59. MacDonald S, Bamforth S, Chen C, Farthing C, Franklyn A, Broadbent C, et al. Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism for haploinsufficiency. Cardiovasc Res. 2008;79:448-57 pubmed publisher
    ..Cardiac malformation associated with Cited2 haploinsufficiency may occur by reducing expression of key Cited2 targets such as Pitx2c. ..
  60. Liu W, Selever J, Lu M, Martin J. Genetic dissection of Pitx2 in craniofacial development uncovers new functions in branchial arch morphogenesis, late aspects of tooth morphogenesis and cell migration. Development. 2003;130:6375-85 pubmed
    b>Pitx2, a paired-related homeobox gene that encodes multiple isoforms, is the gene mutated in the haploinsufficient Rieger Syndrome type 1 that includes dental, ocular and abdominal wall anomalies as cardinal features...
  61. Gherzi R, Trabucchi M, Ponassi M, Gallouzi I, Rosenfeld M, Briata P. Akt2-mediated phosphorylation of Pitx2 controls Ccnd1 mRNA decay during muscle cell differentiation. Cell Death Differ. 2010;17:975-83 pubmed publisher
    Paired-like homeodomain 2 (Pitx2), first identified as the gene responsible for the Axenfeld-Rieger syndrome, encodes a protein factor that, controlling cell proliferation in a tissue-specific manner, has a crucial role in morphogenesis...
  62. Furtado M, Biben C, Shiratori H, Hamada H, Harvey R. Characterization of Pitx2c expression in the mouse heart using a reporter transgene. Dev Dyn. 2011;240:195-203 pubmed publisher
    ..Our data show that the P2Ztg transgene is a useful resource for detection of molecular disturbances in the LR cascade, as well as morphogenetic defects associated with other cardiac congenital disorders. ..
  63. Zhou Y, Liu D, Kaminski H. Pitx2 regulates myosin heavy chain isoform expression and multi-innervation in extraocular muscle. J Physiol. 2011;589:4601-14 pubmed publisher
    ..The paired-like homeodomain transcription factor 2 (Pitx2) is known to regulate the formation of extraocular muscle development and in this report we show that its ..
  64. Diehl A, Zareparsi S, Qian M, Khanna R, Angeles R, Gage P. Extraocular muscle morphogenesis and gene expression are regulated by Pitx2 gene dose. Invest Ophthalmol Vis Sci. 2006;47:1785-93 pubmed
    b>PITX2 gene dose plays a central role in Axenfeld-Rieger syndrome. The purpose of this study was to test the hypothesis that the effects of Pitx2 gene dose on eye development can be molecularly dissected in available Pitx2 mutant mice...
  65. Liu F, Chu E, WATT B, Zhang Y, Gallant N, Andl T, et al. Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev Biol. 2008;313:210-24 pubmed
  66. Nowotschin S, Liao J, Gage P, Epstein J, Campione M, Morrow B. Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart field. Development. 2006;133:1565-73 pubmed
    ..Here, we show that Tbx1 is co-expressed with the bicoid-like homeodomain transcription factor Pitx2 in secondary heart field cells in the pharyngeal mesenchyme...
  67. Liu C, Liu W, Palie J, Lu M, Brown N, Martin J. Pitx2c patterns anterior myocardium and aortic arch vessels and is required for local cell movement into atrioventricular cushions. Development. 2002;129:5081-91 pubmed
    Inactivation of the left-right asymmetry gene Pitx2 has been shown, in mice, to result in right isomerism with associated defects that are similar to that found in humans...
  68. Shih H, Gross M, Kioussi C. Expression pattern of the homeodomain transcription factor Pitx2 during muscle development. Gene Expr Patterns. 2007;7:441-51 pubmed
    Late-stage Pitx2(+/LacZ) mouse embryos stained with x-gal appeared to have blue muscles, suggesting that Pitx2 expression specifically marks some phase of the myogenic progression or muscle anlagen formation...
  69. Marcil A, Dumontier E, Chamberland M, Camper S, Drouin J. Pitx1 and Pitx2 are required for development of hindlimb buds. Development. 2003;130:45-55 pubmed
    Two closely related homeobox transcription factors, Pitx1 and Pitx2, have been implicated in patterning of lateral plate mesoderm derivatives: Pitx1 for specification of hindlimb identity and Pitx2 for determination of laterality...
  70. Norris D, Brennan J, Bikoff E, Robertson E. The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo. Development. 2002;129:3455-68 pubmed
    ..However loss of the ASE disrupts Lefty2 (Leftb) expression and causes delayed Pitx2 expression leading to late onset, relatively minor LR patterning defects...
  71. Gage P, Suh H, Camper S. Dosage requirement of Pitx2 for development of multiple organs. Development. 1999;126:4643-51 pubmed
    b>Pitx2 is a homeodomain transcription factor that is mutated in Rieger syndrome, a haploinsufficiency disorder affecting eyes and teeth. Pitx2 also has a postulated role in left-right axis determination...
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    ..A candidate mediator in mouse, frog and zebrafish embryos is the homeobox gene Pitx2. It is asymmetrically expressed in the left lateral plate mesoderm, tubular heart and early gut tube...
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    b>Pitx2 is a paired-related homeobox gene that has been shown to play a central role during development. In the mouse, there are three isoforms, Pitx2a, b, and c, which differ only in their amino terminal regions...