Gene Symbol: Nkx2-5
Description: NK2 homeobox 5
Alias: Csx, Nkx-2.5, Nkx2.5, tinman, homeobox protein Nkx-2.5, Drosophila NK2 transcription factor related, locus 5, NK2 transcription factor related, locus 5, cardiac-specific homeobox, homeobox protein CSX, homeobox protein NK-2 homolog E
Species: mouse
Products:     Nkx2-5

Top Publications

  1. Douglas Y, Mahtab E, Jongbloed M, Uhrin P, Zaujec J, Binder B, et al. Pulmonary vein, dorsal atrial wall and atrial septum abnormalities in podoplanin knockout mice with disturbed posterior heart field contribution. Pediatr Res. 2009;65:27-32 pubmed publisher
    ..We conclude that myocardium of the PVs, dorsal atrial wall, and atrial septum, as well as the smooth muscle cells, are derived from the posterior heart field regulated by podoplanin. ..
  2. Ma Q, Zhou B, Pu W. Reassessment of Isl1 and Nkx2-5 cardiac fate maps using a Gata4-based reporter of Cre activity. Dev Biol. 2008;323:98-104 pubmed publisher
    ..These results have important implications for our understanding of cardiac lineage diversification in vivo, and for the interpretation of Cre-based fate maps. ..
  3. Liu Y, Asakura M, Inoue H, Nakamura T, Sano M, Niu Z, et al. Sox17 is essential for the specification of cardiac mesoderm in embryonic stem cells. Proc Natl Acad Sci U S A. 2007;104:3859-64 pubmed
    ..Sox17 short-hairpin RNA blocks cardiac myogenesis non-cell autonomously and impairs the induction of Hex, a homeodomain transcription factor that is known to be required for the production of endoderm-derived heart-inducing factors. ..
  4. Xin M, Davis C, Molkentin J, Lien C, Duncan S, Richardson J, et al. A threshold of GATA4 and GATA6 expression is required for cardiovascular development. Proc Natl Acad Sci U S A. 2006;103:11189-94 pubmed
  5. Bruneau B, Nemer G, Schmitt J, Charron F, Robitaille L, Caron S, et al. A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell. 2001;106:709-21 pubmed
  6. Maitra M, Schluterman M, Nichols H, Richardson J, Lo C, Srivastava D, et al. Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development. Dev Biol. 2009;326:368-77 pubmed publisher
    ..These findings highlight the unique genetic interactions of Gata4 and Gata6 with Tbx5 for normal cardiac morphogenesis in vivo. ..
  7. Chan J, Takeda M, Briggs L, Graham M, Lu J, Horikoshi N, et al. Identification of cardiac-specific myosin light chain kinase. Circ Res. 2008;102:571-80 pubmed publisher
    ..Both overexpression and knockdown of cardiac MLCK in cultured cardiomyocytes revealed that cardiac MLCK is likely a new regulator of MLC2 phosphorylation, sarcomere organization, and cardiomyocyte contraction. ..
  8. Ma L, Lu M, Schwartz R, Martin J. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development. 2005;132:5601-11 pubmed
    ..Our data indicate that Bmp2 has a crucial role in coordinating multiple aspects of AV canal morphogenesis. ..
  9. Van Loo P, Mahtab E, Wisse L, Hou J, Grosveld F, Suske G, et al. Transcription factor Sp3 knockout mice display serious cardiac malformations. Mol Cell Biol. 2007;27:8571-82 pubmed
    ..Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development and suggest that it has a crucial role in myocardial differentiation. ..

More Information


  1. Harvey R, Lai D, Elliott D, Biben C, Solloway M, Prall O, et al. Homeodomain factor Nkx2-5 in heart development and disease. Cold Spring Harb Symp Quant Biol. 2002;67:107-14 pubmed
  2. Xu H, Morishima M, Wylie J, Schwartz R, Bruneau B, Lindsay E, et al. Tbx1 has a dual role in the morphogenesis of the cardiac outflow tract. Development. 2004;131:3217-27 pubmed
    ..Furthermore, our data link, for the first time, the function of the secondary heart field to congenital heart disease. ..
  3. Riazi A, Lee H, Hsu C, Van Arsdell G. CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro. J Biol Chem. 2005;280:10716-20 pubmed
    b>CSX/Nkx2.5 transcription factor plays a pivotal role in cardiac development; however, its role in development and differentiation of other organs has not been investigated...
  4. Takeda M, Briggs L, Wakimoto H, Marks M, Warren S, Lu J, et al. Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation. Lab Invest. 2009;89:983-93 pubmed publisher
    ..These results suggest that Nkx2-5 is necessary for proper conduction and contraction after 2 weeks of age, but with a substantially distinct level of necessity at 2 weeks of age compared with that in the perinatal period. ..
  5. Lin Q, Schwarz J, Bucana C, Olson E. Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science. 1997;276:1404-7 pubmed
    ..Thus, MEF2C is an essential regulator of cardiac myogenesis and right ventricular development. ..
  6. Später D, Abramczuk M, Buac K, Zangi L, Stachel M, Clarke J, et al. A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nat Cell Biol. 2013;15:1098-106 pubmed publisher
    ..We conclude that a primary purpose of the FHF is to generate cardiac muscle and support the contractile activity of the primitive heart tube, whereas SHF-derived progenitors contribute to heart cell lineage diversification. ..
  7. Chen H, Shi S, Acosta L, Li W, Lu J, Bao S, et al. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development. 2004;131:2219-31 pubmed
    ..This may provide an underlying mechanism for understanding the pathogenesis of both structural and functional congenital heart defects. ..
  8. Mommersteeg M, Domínguez J, Wiese C, Norden J, de Gier de Vries C, Burch J, et al. The sinus venosus progenitors separate and diversify from the first and second heart fields early in development. Cardiovasc Res. 2010;87:92-101 pubmed publisher
    ..After patterning of the cardiogenic mesoderm, this progenitor population remains spatially separated and genetically distinctive from the second heart field subpopulation. ..
  9. Laforest B, Nemer M. GATA5 interacts with GATA4 and GATA6 in outflow tract development. Dev Biol. 2011;358:368-78 pubmed publisher
    ..The data identify GATA5 as a potential genetic modifier of congenital heart disease and provide insight for elucidating the genetic basis of an important class of human birth defects. ..
  10. Parlakian A, Tuil D, Hamard G, Tavernier G, Hentzen D, Concordet J, et al. Targeted inactivation of serum response factor in the developing heart results in myocardial defects and embryonic lethality. Mol Cell Biol. 2004;24:5281-9 pubmed
    ..5, GATA4, myocardin, and the SRF target gene c-fos prior to overt maldevelopment. We conclude that SRF is crucial for cardiac differentiation and maturation, acting as a global regulator of multiple developmental genes. ..
  11. Caprioli A, Koyano Nakagawa N, Iacovino M, Shi X, Ferdous A, Harvey R, et al. Nkx2-5 represses Gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis. Circulation. 2011;123:1633-41 pubmed publisher
    ..Our results demonstrate that the hematopoietic/erythroid cell fate is suppressed via Nkx2-5 during mesodermal fate determination, and that the Gata1 gene is one of the targets that are suppressed by Nkx2-5. ..
  12. Cai C, Martin J, Sun Y, Cui L, Wang L, Ouyang K, et al. A myocardial lineage derives from Tbx18 epicardial cells. Nature. 2008;454:104-8 pubmed publisher
    ..The pluripotency of Tbx18 proepicardial cells provides a theoretical framework for applying these progenitors to effect cardiac repair and regeneration. ..
  13. Schwartz R, Olson E. Building the heart piece by piece: modularity of cis-elements regulating Nkx2-5 transcription. Development. 1999;126:4187-92 pubmed
    Heart formation in Drosophila is dependent on the homeobox gene tinman. The homeobox gene Nkx2-5 is closely related to tinman and is the earliest known marker for cardiogenesis in vertebrate embryos...
  14. Stennard F, Costa M, Elliott D, Rankin S, Haast S, Lai D, et al. Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Dev Biol. 2003;262:206-24 pubmed
    ..We propose that Tbx20 plays an integrated role in the ancient myogenic program of the heart, and has been additionally coopted during evolution of vertebrates for endocardial cushion development. ..
  15. Koshiba Takeuchi K, Takeuchi J, Arruda E, Kathiriya I, Mo R, Hui C, et al. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nat Genet. 2006;38:175-83 pubmed
    ..Thus, a positive and negative feed-forward circuit between Tbx5 and Sall4 ensures precise patterning of embryonic limb and heart and provides a unifying mechanism for heart/hand syndromes. ..
  16. Zhang Z, Cerrato F, Xu H, Vitelli F, Morishima M, Vincentz J, et al. Tbx1 expression in pharyngeal epithelia is necessary for pharyngeal arch artery development. Development. 2005;132:5307-15 pubmed
    ..We also thereby demonstrate conclusively that the role of Tbx1 in fourth PAA development is cell non-autonomous...
  17. Luxan G, Casanova J, Martínez Poveda B, Prados B, D Amato G, MacGrogan D, et al. Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy. Nat Med. 2013;19:193-201 pubmed publisher
    ..These results implicate NOTCH signaling in LVNC and indicate that MIB1 mutations arrest chamber myocardium development, preventing trabecular maturation and compaction. ..
  18. Tanaka M, Wechsler S, Lee I, Yamasaki N, Lawitts J, Izumo S. Complex modular cis-acting elements regulate expression of the cardiac specifying homeobox gene Csx/Nkx2.5. Development. 1999;126:1439-50 pubmed
    The murine homeobox gene Csx/Nkx2.5 is an evolutionarily highly conserved gene related to the Drosophila tinman gene, which specifies cardiac and visceral mesoderm. Since Csx/Nkx2...
  19. Christoffels V, Grieskamp T, Norden J, Mommersteeg M, Rudat C, Kispert A. Tbx18 and the fate of epicardial progenitors. Nature. 2009;458:E8-9; discussion E9-10 pubmed publisher
  20. Zhou B, Ma Q, Rajagopal S, Wu S, Domian I, RIVERA FELICIANO J, et al. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature. 2008;454:109-13 pubmed publisher
  21. Tanaka M, Chen Z, Bartunkova S, Yamasaki N, Izumo S. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 1999;126:1269-80 pubmed
    Csx/Nkx2.5 is a vertebrate homeobox gene with a sequence homology to the Drosophila tinman, which is required for the dorsal mesoderm specification...
  22. Lickert H, Kutsch S, Kanzler B, Tamai Y, Taketo M, Kemler R. Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm. Dev Cell. 2002;3:171-81 pubmed
    ..We provide evidence that ablation of beta-catenin in embryonic endoderm changes cell fate from endoderm to precardiac mesoderm, consistent with the existence of bipotential mesendodermal progenitors in mouse embryos. ..
  23. Parmar H, Coletta P, Faruque N, Sharpe P. An enhancer sequence directs LacZ expression to developing pharyngeal endoderm in transgenic mice. Genesis. 2001;31:57-63 pubmed
    ..5 showed colocalization with the LacZ-positive cells in the foregut and pharyngeal endoderm. This novel enhancer provides a means of tracking the morphogenetic movement of endodermal cells fated to form the foregut. ..
  24. Christoffels V, Mommersteeg M, Trowe M, Prall O, de Gier de Vries C, Soufan A, et al. Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circ Res. 2006;98:1555-63 pubmed
  25. Toko H, Zhu W, Takimoto E, Shiojima I, Hiroi Y, Zou Y, et al. Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart. J Biol Chem. 2002;277:24735-43 pubmed
    b>Csx/Nkx2-5, which is essential for cardiac development of the embryo, is abundantly expressed in the adult heart. We here examined the role of Csx/Nkx2-5 in the adult heart using two kinds of transgenic mice...
  26. Gottlieb P, Pierce S, Sims R, Yamagishi H, Weihe E, Harriss J, et al. Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Nat Genet. 2002;31:25-32 pubmed
    ..These results indicate that m-Bop is essential for cardiomyocyte differentiation and cardiac morphogenesis. ..
  27. Zeisberg E, Ma Q, Juraszek A, Moses K, Schwartz R, Izumo S, et al. Morphogenesis of the right ventricle requires myocardial expression of Gata4. J Clin Invest. 2005;115:1522-31 pubmed
    ..Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. ..
  28. Watanabe Y, Zaffran S, Kuroiwa A, Higuchi H, Ogura T, Harvey R, et al. Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium. Proc Natl Acad Sci U S A. 2012;109:18273-80 pubmed publisher
    ..Our findings provide a paradigm for transcriptional mechanisms that underlie the changes in regulatory networks during the transition from progenitor state to that of the differentiated tissue. ..
  29. Hidaka K, Shirai M, Lee J, Wakayama T, Kodama I, Schneider M, et al. The cellular prion protein identifies bipotential cardiomyogenic progenitors. Circ Res. 2010;106:111-9 pubmed publisher
    ..Thus, PrP demarcates a population of bipotential cardiomyogenic progenitor cells that can differentiate into cardiac or smooth muscle cells. ..
  30. 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
    ..5. The results presented in this study unravel a novel Tbx1-Pitx2 pathway linking Tbx1 to asymmetric cardiac morphogenesis. ..
  31. Van Handel B, Montel Hagen A, Sasidharan R, Nakano H, Ferrari R, Boogerd C, et al. Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium. Cell. 2012;150:590-605 pubmed publisher
    ..These results reveal unexpected plasticity in embryonic endothelium such that loss of a single master regulator can induce ectopic cardiomyogenesis from endothelial cells. ..
  32. Tian Y, Yuan L, Goss A, Wang T, Yang J, Lepore J, et al. Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development. Dev Cell. 2010;18:275-87 pubmed publisher
    ..These data reveal a molecular pathway regulating the posterior cardiac mesoderm and demonstrate that cardiovascular defects caused by loss of Wnt signaling can be rescued pharmacologically in vivo. ..
  33. Karamboulas C, Dakubo G, Liu J, De Repentigny Y, Yutzey K, Wallace V, et al. Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis. J Cell Sci. 2006;119:4315-21 pubmed
    ..Our results show that MEF2C, or genes containing MEF2 DNA-binding sites, is required for the efficient differentiation of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of MEF2 from Drosophila to mammals. ..
  34. Briggs L, Takeda M, Cuadra A, Wakimoto H, Marks M, Walker A, et al. Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ Res. 2008;103:580-90 pubmed publisher
    ..These results indicate that Nkx2-5 function is critical not only during cardiac development but also in perinatal hearts, by regulating expression of several important gene products involved in conduction and contraction. ..
  35. Lee Y, Shioi T, Kasahara H, Jobe S, Wiese R, Markham B, et al. The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression. Mol Cell Biol. 1998;18:3120-9 pubmed
    ..The cardiac muscle-restricted homeobox protein Csx/Nkx2.5 (Csx) is expressed in the precardiac mesoderm as well as the embryonic and adult heart...
  36. RIVERA FELICIANO J, Tabin C. Bmp2 instructs cardiac progenitors to form the heart-valve-inducing field. Dev Biol. 2006;295:580-8 pubmed
    ..Our results demonstrate that Bmp2 is both necessary and sufficient to specify a field of cardiac progenitor cells as the heart-valve-inducing region amid developing atria and ventricles. ..
  37. Cordes K, Sheehy N, White M, Berry E, Morton S, Muth A, et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009;460:705-10 pubmed publisher
    ..These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells. ..
  38. Liang X, Wang G, Lin L, Lowe J, Zhang Q, Bu L, et al. HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res. 2013;113:399-407 pubmed publisher
  39. Tevosian S, Deconinck A, Tanaka M, Schinke M, Litovsky S, Izumo S, et al. FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium. Cell. 2000;101:729-39 pubmed
    ..Our findings provide the molecular inroad into the induction of coronary vasculature by myocardium in the developing heart. ..
  40. Snarr B, O Neal J, Chintalapudi M, Wirrig E, Phelps A, Kubalak S, et al. Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development. Circ Res. 2007;101:971-4 pubmed
    ..We further demonstrate that abnormal development of the SHF-derived DMP is associated with the pathogenesis of atrioventricular septal defects. These results identify a novel role for the SHF. ..
  41. Ai D, Fu X, Wang J, Lu M, Chen L, Baldini A, et al. Canonical Wnt signaling functions in second heart field to promote right ventricular growth. Proc Natl Acad Sci U S A. 2007;104:9319-24 pubmed
    ..Our findings reveal that Wnt signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium. ..
  42. Liu Z, Li T, Liu Y, Jia Z, Li Y, Zhang C, et al. WNT signaling promotes Nkx2.5 expression and early cardiomyogenesis via downregulation of Hdac1. Biochim Biophys Acta. 2009;1793:300-11 pubmed publisher
    ..Our data suggest that WNT signaling pathway plays important roles in the regulation of Hdac1 during the early stage of cardiomyocyte differentiation and that the downregulation of Hdac1 promotes cardiac differentiation. ..
  43. Kuo C, Morrisey E, Anandappa R, Sigrist K, Lu M, Parmacek M, et al. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev. 1997;11:1048-60 pubmed
    ..However, they define a critical role for GATA4 in regulating the rostral-to-caudal and lateral-to-ventral folding of the embryo that is needed for normal cardiac morphogenesis. ..
  44. Ieda M, Tsuchihashi T, Ivey K, Ross R, Hong T, Shaw R, et al. Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling. Dev Cell. 2009;16:233-44 pubmed publisher
    ..These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation. ..
  45. Kasahara H, Wakimoto H, Liu M, Maguire C, Converso K, Shioi T, et al. Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein. J Clin Invest. 2001;108:189-201 pubmed
    ..Recently, ten heterozygous CSX/NKX2.5 homeoprotein mutations were identified in patients with congenital atrioventricular (AV) conduction defects...
  46. Milgrom Hoffman M, Harrelson Z, Ferrara N, Zelzer E, Evans S, Tzahor E. The heart endocardium is derived from vascular endothelial progenitors. Development. 2011;138:4777-87 pubmed publisher
    ..Collectively, our findings demonstrate that the second heart field contains distinct myocardial and endocardial progenitor populations. We suggest that the endocardium derives, at least in part, from vascular endothelial cells. ..
  47. Skerjanc I, Petropoulos H, Ridgeway A, Wilton S. Myocyte enhancer factor 2C and Nkx2-5 up-regulate each other's expression and initiate cardiomyogenesis in P19 cells. J Biol Chem. 1998;273:34904-10 pubmed
    ..These findings indicate the presence of a positive regulatory network between Nkx2-5 and MEF2C and show that both factors can direct early stages of cell differentiation into a cardiomyogenic pathway. ..
  48. Shirai M, Osugi T, Koga H, Kaji Y, Takimoto E, Komuro I, et al. The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis. J Clin Invest. 2002;110:177-84 pubmed
    ..In Rae28(-/-) embryos, expression of the cardiac selector gene Nkx2.5/Csx (Nkx2.5) was initiated properly but was not sufficiently sustained later in development...
  49. Jay P, Harris B, Maguire C, Buerger A, Wakimoto H, Tanaka M, et al. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest. 2004;113:1130-7 pubmed
    ..Postnatal conduction defects in Nkx2-5 mutation may result at least in part from a defect in the genetic program that governs the recruitment or retention of embryonic cardiac myocytes in the conduction system. ..
  50. He A, Ma Q, Cao J, von Gise A, Zhou P, Xie H, et al. Polycomb repressive complex 2 regulates normal development of the mouse heart. Circ Res. 2012;110:406-15 pubmed publisher
    ..Our study reveals a previously undescribed role of EZH2 in regulating heart formation and shows that perturbation of the epigenetic landscape early in cardiogenesis has sustained disruptive effects at later developmental stages. ..
  51. Yin Z, Haynie J, Yang X, Han B, Kiatchoosakun S, Restivo J, et al. The essential role of Cited2, a negative regulator for HIF-1alpha, in heart development and neurulation. Proc Natl Acad Sci U S A. 2002;99:10488-93 pubmed
    ..These findings demonstrate that Cited2 is an indispensable regulatory gene during prenatal development. ..
  52. Biben C, Weber R, Kesteven S, Stanley E, McDonald L, Elliott D, et al. Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5. Circ Res. 2000;87:888-95 pubmed
    ..Our data demonstrate that the complex effects of Nkx2-5 haploinsufficiency in mice are weaker but convergent with those in humans. As in the mouse, the phenotype of human NKX2-5 mutations may be modulated by interacting alleles. ..
  53. Tanaka M, Berul C, Ishii M, Jay P, Wakimoto H, Douglas P, et al. A mouse model of congenital heart disease: cardiac arrhythmias and atrial septal defect caused by haploinsufficiency of the cardiac transcription factor Csx/Nkx2.5. Cold Spring Harb Symp Quant Biol. 2002;67:317-25 pubmed
  54. Self M, Geng X, Oliver G. Six2 activity is required for the formation of the mammalian pyloric sphincter. Dev Biol. 2009;334:409-17 pubmed publisher
    ..5, Sox9, and Gremlin) also appear to be required for the formation of this structure in mammals. Thus, we propose that Six2 activity regulates this gene network during the genesis of the pyloric sphincter in the mouse...
  55. Moses K, DeMayo F, Braun R, Reecy J, Schwartz R. Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice. Genesis. 2001;31:176-80 pubmed
    ..The Nkx2-5/Cre mouse model should provide a useful genetic resource to elucidate the role of loxP manipulated genetic targets in cardiogenesis and other developmental processes. ..
  56. Costello I, Pimeisl I, Dräger S, Bikoff E, Robertson E, Arnold S. The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation. Nat Cell Biol. 2011;13:1084-91 pubmed publisher
    ..Collectively, our experiments demonstrate that Eomes governs discrete context-dependent transcriptional programmes that sequentially specify cardiac and definitive endoderm progenitors during gastrulation. ..
  57. Biben C, Harvey R. Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development. Genes Dev. 1997;11:1357-69 pubmed
    ..One aspect of the intrinsic response to L/R information falls under Nkx2-5 homeobox control. ..
  58. 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. ..
  59. Kim E, Chen L, Ma Y, Yu W, Chang J, Moskowitz I, et al. Expression of sumoylation deficient Nkx2.5 mutant in Nkx2.5 haploinsufficient mice leads to congenital heart defects. PLoS ONE. 2011;6:e20803 pubmed publisher
    Nkx2.5 is a cardiac specific homeobox gene critical for normal heart development. We previously identified Nkx2.5 as a target of sumoylation, a posttranslational modification implicated in a variety of cellular activities...
  60. Christoffels V, Habets P, Franco D, Campione M, de Jong F, Lamers W, et al. Chamber formation and morphogenesis in the developing mammalian heart. Dev Biol. 2000;223:266-78 pubmed
  61. Goddeeris M, Schwartz R, Klingensmith J, Meyers E. Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development. Development. 2007;134:1593-604 pubmed
    ..Disruption of any of these steps can result in a single OFT phenotype. ..
  62. Niu Z, Yu W, Zhang S, Barron M, Belaguli N, Schneider M, et al. Conditional mutagenesis of the murine serum response factor gene blocks cardiogenesis and the transcription of downstream gene targets. J Biol Chem. 2005;280:32531-8 pubmed
  63. Srivastava D, Thomas T, Lin Q, Kirby M, Brown D, Olson E. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet. 1997;16:154-60 pubmed
  64. Tanaka M, Schinke M, Liao H, Yamasaki N, Izumo S. Nkx2.5 and Nkx2.6, homologs of Drosophila tinman, are required for development of the pharynx. Mol Cell Biol. 2001;21:4391-8 pubmed
    Nkx2.5 and Nkx2.6 are murine homologs of Drosophila tinman. Their genes are expressed in the ventral region of the pharynx at early stages of embryogenesis...
  65. Smart N, Risebro C, Melville A, Moses K, Schwartz R, Chien K, et al. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2007;445:177-82 pubmed
  66. Moskowitz I, Kim J, Moore M, Wolf C, Peterson M, Shendure J, et al. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell. 2007;129:1365-76 pubmed
    ..We conclude that a molecular pathway including Tbx5, Nkx2-5, and Id2 coordinates specification of ventricular myocytes into the ventricular conduction system lineage. ..
  67. Molkentin J, Lin Q, Duncan S, Olson E. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. 1997;11:1061-72 pubmed
    ..We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP. ..
  68. Oka T, Maillet M, Watt A, Schwartz R, Aronow B, Duncan S, et al. Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circ Res. 2006;98:837-45 pubmed
    ..Thus, GATA4 is a necessary regulator of cardiac gene expression, hypertrophy, stress-compensation, and myocyte viability. ..
  69. Tian X, Hu T, Zhang H, He L, Huang X, Liu Q, et al. Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries. Cell Res. 2013;23:1075-90 pubmed publisher
    ..Collectively, these data suggested that subepicardial ECs are the major source of intramyocardial coronary arteries in the ventricle wall, and that coronary arteries and veins have a common origin in the developing heart. ..
  70. Zhang Y, Li S, Yuan L, Tian Y, Weidenfeld J, Yang J, et al. Foxp1 coordinates cardiomyocyte proliferation through both cell-autonomous and nonautonomous mechanisms. Genes Dev. 2010;24:1746-57 pubmed publisher
    ..These data show that Foxp1 coordinates the balance of cardiomyocyte proliferation and differentiation through cell lineage-specific regulation of Fgf ligand and Nkx2.5 expression. ..
  71. Komada M, Soriano P. Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis. Genes Dev. 1999;13:1475-85 pubmed
    ..The vesicular localization of Hrs was disrupted in cells treated with wortmannin, implicating Hrs in the phosphatidylinositol 3-kinase pathway of membrane trafficking. ..
  72. Habets P, Moorman A, Clout D, van Roon M, Lingbeek M, Van Lohuizen M, et al. Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation. Genes Dev. 2002;16:1234-46 pubmed
    ..5 on the ANF TBE-NKE, and was able to repress ANF promoter activity. Our data provide a potential mechanism for chamber-restricted gene activity in which the cooperative action of Tbx2 and Nkx2.5 inhibits expression in the AVC. ..
  73. Prall O, Menon M, Solloway M, Watanabe Y, Zaffran S, Bajolle F, et al. An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell. 2007;128:947-59 pubmed
  74. Blaschke R, Hahurij N, Kuijper S, Just S, Wisse L, Deissler K, et al. Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development. Circulation. 2007;115:1830-8 pubmed
    ..From these results, we postulate a critical function of Shox2 in the recruitment of sinus venosus myocardium comprising the sinoatrial nodal region. ..
  75. Stanley E, Biben C, Elefanty A, Barnett L, Koentgen F, Robb L, et al. Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3'UTR-ires-Cre allele of the homeobox gene Nkx2-5. Int J Dev Biol. 2002;46:431-9 pubmed
    ..Our data suggest that the Nkx2-5IRESCre strain will be useful for genetic dissection of the multiple tiers of lineage allocation to the forming heart as well as of molecular interactions within the heart fields and heart tube. ..
  76. Winston J, Erlich J, Green C, Aluko A, Kaiser K, Takematsu M, et al. Heterogeneity of genetic modifiers ensures normal cardiac development. Circulation. 2010;121:1313-21 pubmed publisher
    ..In a genetically heterogeneous population, the predominant effect of modifier genes is health. (Circulation. 2010;121:1313-1321.) ..
  77. Sun Y, Liang X, Najafi N, Cass M, Lin L, Cai C, et al. Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells. Dev Biol. 2007;304:286-96 pubmed
    ..Our studies suggest a role for Isl1 in these distinct domains of expression within the heart. ..
  78. Chinchilla A, Daimi H, Lozano Velasco E, Domínguez J, Caballero R, Delpón E, et al. PITX2 insufficiency leads to atrial electrical and structural remodeling linked to arrhythmogenesis. Circ Cardiovasc Genet. 2011;4:269-79 pubmed publisher
  79. Garg V, Kathiriya I, Barnes R, Schluterman M, King I, Butler C, et al. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature. 2003;424:443-7 pubmed
    ..These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5. ..
  80. Brown C, Chi X, Garcia Gras E, Shirai M, Feng X, Schwartz R. The cardiac determination factor, Nkx2-5, is activated by mutual cofactors GATA-4 and Smad1/4 via a novel upstream enhancer. J Biol Chem. 2004;279:10659-69 pubmed
    The mammalian homologue of Drosophila tinman, Nkx2-5, plays an early role in regulating cardiac genes and morphogenesis...
  81. Zhou B, von Gise A, Ma Q, RIVERA FELICIANO J, Pu W. Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium. Biochem Biophys Res Commun. 2008;375:450-3 pubmed publisher
    ..Taken together, these results suggest that Nkx2-5 and/or Isl1 cardiac progenitors contribute to proepicardium during heart development. ..