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Epithelial-Mesenchymal Transformation in the Embryonic Heart

  • Chapter
Rise and Fall of Epithelial Phenotype

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

The progenitors of the mitral and tricuspid valves and the membranous interventricular septum in the heart arise by an epithelial-mesenchymal cell transformation (EMT) from embryonic endothelial cells. Experiments using collagen gel cultures to mimic the three dimensional environment in the embryonic heart cushions showed that EMT was triggered by an inductive stimulus produced by the adjacent myocardium and that myocardium from a nontransforming region was insufficient to induce transformation. Studies using chick embryos have demonstrated distinct and sequential roles for two isoforms of TGFβ, Bone Morphogenetic Proteins, and roles for several TGFβ-family receptors in this EMT. Additional studies have identified at least two separate transcription factors required for EMT, Slug and Mox-1. The complexity of the inductive signal is not yet fully understood, but recent studies have shown roles for several Wnt proteins and a requirement for signaling by extracellular hyaluronan. The embryonic heart provides an experimental model of relevance to congenital heart diseases that are likely to continue to provide novel insight into the regulation of EMT as a normal process of development.

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References

  1. Eisenberg LM, Markwald RR. Molecular regulation of atrioventricular valvuloseptal morphogenesis. Circulation Research Jul 1995; 77(1):1–6.

    CAS  Google Scholar 

  2. Barry A. The functional significance of the cardiac jelly in the tubular heart of the chick embryo. Anatomical Record 1948; 102:289–298.

    PubMed  CAS  Google Scholar 

  3. Markwald RR, Fitzharris TP, Manasek FJ. Structural development of endocardial cushions. American J Anatomy 1977; 148(1):85–120.

    CAS  Google Scholar 

  4. Markwald RR, Fitzharris TP, Smith WN. Structural analysis of endocardial cytodifferentiation. Dev Biol 1975; 42(1):160–180.

    PubMed  CAS  Google Scholar 

  5. Manasek F. Glycoprotein synthesis and tissue interactions during establishment of the functional embryonic chick heart. J Mol Cell Cardiol 1976; 8:389–402.

    PubMed  CAS  Google Scholar 

  6. Manasek F. Heart development: Interactions involved in cardiac morphogenesis. In: Poste G, Nicholson G, eds. The Cell Surface in Animal Embryogenesis and Development. Elsevier/North-Holland Biomedical Press, 1976:545–598.

    Google Scholar 

  7. Kinsella M, Fitzharris T. Origin of cushion tissue in the developing chick heart: Cinematographic recordings of in situ formation. Science 1980; 207:1359–1360.

    PubMed  CAS  Google Scholar 

  8. van den Hoff MJB, Moorman AFM, Ruijter JM et al. Myocardialization of the cardiac outflow tract. Dev Biol Aug 15 1999; 212(2):477–490.

    Google Scholar 

  9. Hamburger V, Hamilton HL. A series of normal stages in the development of the chick embryo. J Morphol 1951; 88:49–92.

    Google Scholar 

  10. Krug EL, Runyan RB, Markwald RR. Protein extracts from early embryonic hearts initiate cardiac endothelial cytodifferentiation. Dev Biol 1985; 112(2):414–426.

    PubMed  CAS  Google Scholar 

  11. Markwald RR, Fitzharris T, Bolender DL et al. Structural analysis of cell: Matrix association during the morphogenesis of atrioventricular cushion tissue. Dev Biol 1979; 69:634–654.

    PubMed  CAS  Google Scholar 

  12. Bolender DL, Markwald RR. Epithelial-mesenchymal transformation in chick atrioventricular cushion morphogenesis. SEM 1979; (3):313–321.

    Google Scholar 

  13. Icardo JM, Ojeda JL, Hurle JM. Endocardial cell polarity During the looping of the heart in the chick-embryo. Dev Biol 1982; 90(1):203–209.

    PubMed  CAS  Google Scholar 

  14. Markwald RR, Fitzharris T, Bank H et al. Structural analysis on the matrical organization of glycosaminoglycans in developing endocardial cushions. Dev Biol 1978; 62(2):292–316.

    PubMed  CAS  Google Scholar 

  15. Kitten GT, Kolker SJ, Krob SL et al. Type VI collagen in the cardiac valves and connective tissue septa during heart development. Braz J Med Biol Res 1996; 29:1189–1193.

    PubMed  CAS  Google Scholar 

  16. De La Cruz M, Gimenez-ribotta M, Saravalli O. The contribution of the inferior endocardial cushion of the atrioventricular canal to cardiac septation and to the development of the atrioventricular valve: Study in the chick embryo. Am J Physiol Regul Integr Comp Physiol 1983; 166:63–72.

    Google Scholar 

  17. Elsdale T, Bard J. Collagen substrata for studies on cell behavior. J Cell Biol 1972; 54:626–637.

    PubMed  CAS  Google Scholar 

  18. Schor S. Cell proliferation and migration on collagen substrata in vitro. J Cell Sci 1980; 41:159–175.

    PubMed  CAS  Google Scholar 

  19. Greenburg G, Hay ED. Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells. J Cell Biol 1982; 95:333–339.

    PubMed  CAS  Google Scholar 

  20. Bernanke DH, Markwald RR. Migratory behavior of cardiac cushion tissue-cells in a collagen-lattice culture system. Dev Biol 1982; 91(2):235–245.

    PubMed  CAS  Google Scholar 

  21. Bemanke DH, Markwald RR. Effects of hyaluronic acid on cardiac cushion tissue cells in collagen matrix cultures. Texas Reports in Biology and Medicine 1979; 39:271–285.

    Google Scholar 

  22. Overton J. Differential response of embryonic-cells to culture on tissue matrices. Tissue & Cell 1979; 11(1):89–98.

    CAS  Google Scholar 

  23. Runyan RB, Markwald RR. Invasion of mesenchyme into three-dimensional collagen gels: A regional and temporal analysis of interaction in embryonic heart tissue. Dev Biol 1983; 95(1):108–114.

    PubMed  CAS  Google Scholar 

  24. Mjaatvedt CH, Lepera RC, Markwald RR. Myocardial specificity for initiating endothelial-mesenchymal cell transition in embryonic chick heart correlates with a particulate distribution of fibronectin. Dev Biol 1987; 119(1):59–67.

    PubMed  CAS  Google Scholar 

  25. Krug EL, Mjaatvedt CH, Markwald RR. Extracellular matrix from embryonic myocardium elicits an early morphogenetic event in cardiac endothelial differentiation. Dev Biol 1987; 120(2):348–355.

    PubMed  CAS  Google Scholar 

  26. Mjaatvedt CH, Markwald RR. Induction of an epithelial-mesenchymal transition by an in vivo adheron-like complex. Dev Biol 1989; 136(1):118–128.

    PubMed  CAS  Google Scholar 

  27. Potts JD, Runyan RB. Epithelial-mesenchymal cell transformation in the embryonic heart can be mediated, in part, by transforming growth factor beta. Dev Biol 1989; 134(2):392–401.

    PubMed  CAS  Google Scholar 

  28. Camenisch TD, Schroeder JA, Bradley J et al. Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. Nat Med 2002; 8(8):850–855.

    PubMed  CAS  Google Scholar 

  29. Walsh E, Stainier DYR. Novel role for glycosaminoglycans in cell signaling events during heart valve initiation: Cloning of the zebrafish jekyll mutation. Dev Biol 2001; 235(1):229–229.

    Google Scholar 

  30. Gassmann M, Casagranda F, Orioli D et al. Aberrant neural and cardiac development in mice lacking the Erbb4 neuregulin receptor. Nature 1995; 378(6555):390–394.

    PubMed  CAS  Google Scholar 

  31. Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. Nature 1995;378(6555):386–390.

    PubMed  CAS  Google Scholar 

  32. Mjaatvedt CH, Krug EL, Markwald RR. An antiserum (ES1) against a particulate form of extracellular matrix blocks the transition of cardiac endothelium into mesenchyme in culture. Dev Biol 1991; 145(2):219–230.

    PubMed  CAS  Google Scholar 

  33. Sinning AR, Krug EL, Markwald RR. Multiple glycoproteins localize to a particulate form of extracellular matrix in regions of the embryonic heart where endothelial cells transform into mesenchyme. Anatomical Record 1992; 232(2):285–292.

    PubMed  CAS  Google Scholar 

  34. Rezaee M, Isokawa K, Halligan N et al. Identification of an extracellular 130-kDa protein involved in early cardiac morphogenesis. J Biol Chem 1993; 268(19):14404–14411.

    PubMed  CAS  Google Scholar 

  35. Isokawa K, Rezaee M, Wunsch A et al. Identification of transferrin as one of multiple EDTA-extractable extracellular proteins involved in early chick heart morphogenesis. J Cell Biochem 1994; 54:207–218.

    PubMed  CAS  Google Scholar 

  36. Sinning AR. Partial purification of HLAMP-1 provides direct evidence for the multicomponent nature of the particulate matrix associated with cardiac mesenchyme formation. J Cell Biochem 1997; 66(1):112–122.

    PubMed  CAS  Google Scholar 

  37. Roberts A, Flanders K, Kondaiah P et al. Transforming growth factor β: Biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm Res 1988;44:157–197.

    PubMed  CAS  Google Scholar 

  38. Nakajima Y, Krug EL, Markwald RR. Myocardial regulation of transforming growth factor-β expression by outflow tract endothelium in the early embryonic chick heart. Dev Biol 1994;165:615–626.

    PubMed  CAS  Google Scholar 

  39. Burt DW. Evolutionary grouping of the transforming growth factor-β superfamily. Biochem Biophys Res Commun 1992; 184(2):590–595.

    PubMed  CAS  Google Scholar 

  40. Potts JD, Vincent EB, Runyan RB et al. Sense and antisense TGF-Beta 3 messenger-RNA levels correlate with cardiac-valve induction. Dev Dyn 1992; 193(4):340–345.

    PubMed  CAS  Google Scholar 

  41. Akhurst RJ, Lehnert S, Faissner A et al. TGF beta in murine morphogenetic processes: The early embryo and cardiogenesis. Development 1990; 108(4):645–656.

    PubMed  CAS  Google Scholar 

  42. Dickson MC, Slager HG, Duffie E et al. RNA and protein localisations of TFG beta 2 in the early mouse embryo. Development 1993; 117:625–639.

    PubMed  CAS  Google Scholar 

  43. Camenisch TD, Molin DGM, Person A et al. Temporal and distinct TGF beta ligand requirements during mouse and avian endocardial cushion morphogenesis. Dev Biol 2002; 248(1):170–181.

    PubMed  CAS  Google Scholar 

  44. Barnett JV, Moustakas A, Lin W et al. Cloning and developmental expression of the chick type II and type III TGF beta receptors. Dev Dyn 1994; 199(1): 12–27.

    PubMed  CAS  Google Scholar 

  45. Boyer AS, Ayerinskas II, Vincent EB et al. TGF beta 2 and TGF beta 3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. Dev Biol 1999; 208(2):530–545.

    PubMed  CAS  Google Scholar 

  46. Potts JD, Dagle JM, Walder JA et al. Epithelial mesenchymal transformation of embryonic cardiac endothelial-cells is inhibited by a modified antisense oligodeoxynudeotide to transforming growth factor beta 3. Proc Nat Acad Sci USA 1991; 88(4):1516–1520.

    PubMed  CAS  Google Scholar 

  47. Diebold RJ, Eis MJ, Yin M et al. Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated. Proc Nat Acad Sci USA 1995;92(26):12215–12219.

    PubMed  CAS  Google Scholar 

  48. Proetzel G, Pawlowski SA, Wiles MV et al. Transforming growth factor-beta 3 is required for secondary palate fusion. Nat Genet 1995;11(4):409–414.

    PubMed  CAS  Google Scholar 

  49. Sanford LP, Ormsby I, Gittenberger-de Groot AC et al. TGFβ2 knockout mice have multiple development defects that are non overlapping with other TGFβ knockout phenotypes. Development 1997;124:2659–2670.

    PubMed  CAS  Google Scholar 

  50. Massague J. TGFβ signaling: Receptors, transducers, and Mad proteins. Cell 1996;85:947–950.

    PubMed  CAS  Google Scholar 

  51. Wrana JL, Attisano L, Wieser R et al. Mechanism of activation of the TGF-β receptor. Nature 1994;370:341–347.

    PubMed  CAS  Google Scholar 

  52. Wrana JL, Attisano L, Carcamo J et al. TGF beta signals through a heteromeric protein kinase receptor complex. Cell 1992;71:1003–1014.

    PubMed  CAS  Google Scholar 

  53. Lopez-Casillas F, Wrana JL, Massague J. Betaglycan presents ligand to the TGF beta signaling receptor. Cell 1993;73(7):1435–1444.

    PubMed  CAS  Google Scholar 

  54. Barnett JV, Moustakas A, Lin W et al. Cloning and developmental expression of the chick type II and type III TGF⇓ receptors. Dev Dyn 1994;199:12–27.

    PubMed  CAS  Google Scholar 

  55. Brown CB, Boyer AS, Runyan RB et al. Antibodies to the type II TGF beta receptor block cell activation and migration during atrioventricular cushion transformation in the heart. Dev Biol 1996;174(2):248–257.

    PubMed  CAS  Google Scholar 

  56. Brown CB, Boyer AS, Runyan RB et al. Requirement of type III TGF-beta receptor for endocardial cell transformation in the heart. Science 1999;283(5410):2080–2082.

    PubMed  CAS  Google Scholar 

  57. Boyer AS, Runyan RB. TGFβ Type III and TGFβ Type II receptors have distinct activities during epithelial-mesenchymal cell transformation in the embryonic heart. Dev Dyn 2001;221(4):454–459.

    PubMed  CAS  Google Scholar 

  58. Massague J. The transforming growth factor-beta family. Ann Rev Cell Biol 1990;6:597–641.

    Article  PubMed  CAS  Google Scholar 

  59. Annes JP, Munger JS, Rifkin DB. Making sense of latent TGF beta activation. J Cell Sci 2003;116(2):217–224.

    PubMed  CAS  Google Scholar 

  60. Ghosh S, Brauer PR. Latent transforming growth factor-β is present in the extracellular matrix of embryonic hearts in situ. Dev Dyn 1996;205(2):126–134.

    PubMed  CAS  Google Scholar 

  61. McCormick KM. TGF beta 2 activation status during cardiac morphogenesis. Dev Dyn 2001;222(1):17–25.

    PubMed  CAS  Google Scholar 

  62. Nakajima Y, Miyazono K, Kato M et al. Extracellular fibrillar structure of latent TGF beta binding protein-1: Role in TGF beta-dependent endothelial-mesenchymal transformation during endocardial cushion tissue formation in mouse embryonic heart. J Cell Biol 1997;136(1):193–204.

    PubMed  CAS  Google Scholar 

  63. McGuire PG, Orkin RW. Urokinase activity in the developing avian heart: A spatial and temporal analysis. Dev Dyn 1992;193:24–33.

    PubMed  CAS  Google Scholar 

  64. Alexander SM, Jackson KJ, Bushnell KM et al. Spatial and temporal expression of the 72-kDa type IV collagenase (MMP-2) correlates with development and differentiation of valves in the embryonic avian heart. Dev Dyn 1997;209(3):261–268.

    PubMed  CAS  Google Scholar 

  65. McGuire PG, Alexander SM. Urokinase production by embryonic endocardial-derived cells: Regulation by substrate composition. Dev Biol (Orlando) 1993;155(2):442–451.

    PubMed  CAS  Google Scholar 

  66. Bouchey D, Argraves WS, Little CD. Fibulin-1, vitronectin, and fibronectin expression during avian cardiac valve and septa development. Anat Rec 1996;244(4):540–551.

    PubMed  CAS  Google Scholar 

  67. Kitten GT, Markwald RR, Bolender DL. Distribution of basement membrane antigens in cryopreserved early embryonic hearts. Anat Rec 1987;217(4):379–390.

    PubMed  CAS  Google Scholar 

  68. Mjaatvedt CH, Yamamura H, Capehart AA et al. The Cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation. Dev Biol (Orlando) 1998;202(1):56–66.

    PubMed  CAS  Google Scholar 

  69. Yamamura H, Zhang M, Markwald RR et al. A heart segmental defect in the anterior-posterior axis of a transgenic mutant mouse. Dev Biol (Orlando) 1997;186(1):58–72.

    PubMed  CAS  Google Scholar 

  70. Baldwin HS, Lloyd TR, Solursh M. Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ. Circ Res 1994;74(2):244–252.

    PubMed  CAS  Google Scholar 

  71. Camenisch TD, Biesterfeldt J, Brehm-Gibson T et al. Regulation of cardiac cushion development by hyaluronan. Exp Clin Cardiol 2001;6:4–10.

    CAS  Google Scholar 

  72. Camenisch TD, Spicer AP, Brehm-Gibson T et al. Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. J Clin Invest 2000;106(3):349–360.

    PubMed  CAS  Google Scholar 

  73. Klewer SE, Krob SL, Kolker SJ et al. Expression of type VI collagen in the developing mouse heart. Dev Dyn 1998;211(3):248–255.

    PubMed  CAS  Google Scholar 

  74. DiMilla PA, Stone JA, Quinn JA et al. Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength. J Cell Biol 1993;122(3):729–737.

    PubMed  CAS  Google Scholar 

  75. McDonald JA. Integrins minireview series. J Biol Chem 2000;275(29):21783.

    PubMed  CAS  Google Scholar 

  76. Palecek SP, Loftus JC, Ginsberg MH et al. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. [erratum appears in Nature 1997; 388(6638):210.]. Nature 1997;385(6616):537–540.

    PubMed  CAS  Google Scholar 

  77. Akiyama SK, Nagata K, Yamada K. Cell surface receptors for extracellular matrix components. Biochimica et Biophysica Acta 1990;1031:91–110.

    PubMed  CAS  Google Scholar 

  78. Duband JL, Dufour S, Yamada SS et al. Neural crest cell locomotion induced by antibodies to beta 1 integrins. A tool for studying the roles of substratum molecular avidity and density in migration. J Cell Sci 1991;98 (Pt 4):517–532.

    PubMed  CAS  Google Scholar 

  79. Kuijpers TW, Mul EP, Blom M et al. Freezing adhesion molecules in a state of high-avidity binding blocks eosinophil migration. Journal of Experimental Medicine 1993;178(1):279–284.

    PubMed  CAS  Google Scholar 

  80. Keely PJ, Fong AM, Zutter MM et al. Alteration of collagen-dependent adhesion, motility, and morphogenesis by the expression of antisense alpha 2 integrin mRNA in mammary cells. J Cell Sci 1995;108 (Pt 2):595–607.

    PubMed  CAS  Google Scholar 

  81. Giancotti FG, Ruoslahti E. Integrin signaling. Science 1999;285(5430):1028–1032.

    PubMed  CAS  Google Scholar 

  82. Loeber CP, Runyan RB. A comparison of fibronectin, laminin, and galactosyltransferase adhesion mechanisms during embryonic cardiac mesenchymal cell-migration in vitro. Dev Biol Aug 1990;140(2):401–412.

    CAS  Google Scholar 

  83. Ladher RK, Church VL, Allen S et al. Cloning and expression of the Wnt antagonists Sfrp-2 and Frzb during chick development. Dev Biol 2000;218(2):183–198.

    PubMed  CAS  Google Scholar 

  84. Lyons KM, Pelton RW, Hogan BL. Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A). Development 1990;109(4):833–844.

    PubMed  CAS  Google Scholar 

  85. Yamagishi T, Nakajima Y, Miyazono K et al. Bone morphogenetic protein-2 acts synergistically with transforming growth factor-beta 3 during endothelial-mesenchymal transformation in the developing chick heart. J Cell Physiol 1999;180(1):35–45.

    PubMed  CAS  Google Scholar 

  86. Nakajima Y, Yamagishi T, Hokari S et al. Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: Roles of transforming growth factor (TGF)-beta and bone morphogenetic protein (BMP). Anat Rec 2000;258(2):119–127.

    PubMed  CAS  Google Scholar 

  87. Kim RY, Robertson EJ, Solloway MJ. Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Dev Biol 2001;235(2):449–466.

    PubMed  CAS  Google Scholar 

  88. Allen SP, Bogardi JP, Barlow AJ et al. Misexpression of noggin leads to septal defects in the outflow tract of the chick heart. Dev Biol 2001;235(1):98–109.

    PubMed  CAS  Google Scholar 

  89. Runyan RB, Potts JD, Sharma RV et al. Signal transduction of a tissue interaction during embryonic heart development. Cell Regul 1990;1(3):301–313.

    PubMed  CAS  Google Scholar 

  90. Lakkis MM, Epstein JA. Neurofibromin modulation of ras activity is required for normal endocardial-mesenchymal transformation in the developing heart. Development-Supplement 1998;125(22):4359–4367.

    CAS  Google Scholar 

  91. Garcia-Castro MI, Vielmetter E, Bronner-Fraser M. N-cadherin, a cell adhesion molecule involved in establishment of embryonic left-right asymmetry. Science 2000;288(5468):1047–1051.

    PubMed  CAS  Google Scholar 

  92. Breier G, Albrecht U, Sterrer S et al. Expression of vascular endothelial growth-factor during embryonic angiogenesis and endothelial-cell differentiation. Development 1992;114(2):521–532.

    PubMed  CAS  Google Scholar 

  93. Linask KK, ImanakaYoshida K, Knudsen KA. N-cadherin/beta-catenin interaction is necessary for chick cardiomyocyte compartmentalization and myofibrillogenesis. Dev Biol 1997;186(2):B65–B65.

    Google Scholar 

  94. Caveda L, Martin-Padura I, Navarro P et al. Inhibition of cultured cell growth by vascular endothelial cadherin (cadherin-5/VE-cadherin). J Clin Invest 1996;98(4):886–893.

    Article  PubMed  CAS  Google Scholar 

  95. Coffin JD, Harrison J, Schwartz S et al. Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo. Dev Biol 1991;148(1):51–62.

    PubMed  CAS  Google Scholar 

  96. Nieto MA, Sargent MG, Wilkinson DG et al. Control of cell behavior during vertebrate development by slug, a zinc finger gene. Science 1994;264:835–839.

    PubMed  CAS  Google Scholar 

  97. Romano LA, Runyan RB. Slug is a mediator of epithelial-mesenchymal cell transformation in the developing chicken heart. Dev Biol 1999;212(1):243–254.

    PubMed  CAS  Google Scholar 

  98. Romano LA, Runyan RB. Slug is an essential target of TGFbeta2 signaling in the developing chicken heart. Dev Biol 2000;223(1):91–102.

    PubMed  CAS  Google Scholar 

  99. Cano A, Perez-Moreno MA, Rodrigo I et al. The transcription factor Snail controls epithelialmesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol FEB 2000;2(2):76–83.

    CAS  Google Scholar 

  100. Yokoyama K, Kamata N, Fujimoto R et al. Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas. Int J Oncol 2003;22(4):891–898.

    PubMed  CAS  Google Scholar 

  101. Candia AF, Hu J, Crosby J et al. Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development 1992;116(4):1123–1136.

    PubMed  CAS  Google Scholar 

  102. Bayna EM, Runyan RB, Scully NF et al. Cell-surface galactosyltransferase as a recognition molecule during development. Mol Cell Biochem 1986;72(1–2):141–151.

    PubMed  CAS  Google Scholar 

  103. Herrmann BG, Lehrach H. From phenotype to gene: Molecular cloning in the Brachyury (T) locus region. Curr Top Microbiol Immunol 1988;137:77–81.

    PubMed  CAS  Google Scholar 

  104. de la Pompa JL, Timmerman LA, Takimoto H et al. Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum [see comments]. Nature 1998;392(6672):182–186.

    PubMed  Google Scholar 

  105. Ranger AM, Grusby MJ, Hodge MR et al. The transcription factor NF-ATc is essential for cardiac valve formation. Nature 1998;392(6672):186–190.

    PubMed  CAS  Google Scholar 

  106. Molkentin JD, Lu JR, Antos CL et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 1998;93(2):215–228.

    PubMed  CAS  Google Scholar 

  107. Evans SM, Obrien TX. Expression of the helix-loop-helix factor id during mouse embryonic-development. Dev Biol 1993;159(2):485–499.

    PubMed  CAS  Google Scholar 

  108. Kelley C, Blumberg H, Zon LI et al. GATA-4 is a novel transcription factor expressed in endocardium of the developing heart. Development 1993;118(3):817–827.

    PubMed  CAS  Google Scholar 

  109. Ferencz C, Rubin JD, Mccarter RJ et al. Congenital heart disease: Prevalence at livebirth; the Baltimore Washington infant study. Am J Epidem 1990;121:31–36.

    Google Scholar 

  110. Carmi R, Boughman JA, Ferencz C. Endocardial cushion defect: Further studies of “isolated” versus “syndromic” occurrence. Am J Med Genet 1992;43(3):569–575.

    PubMed  CAS  Google Scholar 

  111. Korenberg JR, Bradley C, Disteche CM. Down Syndrome: Molecular mapping of the congenital heart disease and duodenal stenosis. Am J Hum Genet 1992;50:294–302.

    PubMed  CAS  Google Scholar 

  112. Adams MM, Erickson JD, Layde PM et al. Down’s syndrome. Recent trends in the United States. JAMA 1981;246(7):758–760.

    PubMed  CAS  Google Scholar 

  113. Kurnit D, Aldridge J, Matsuoka R et al. Increased adhesiveness of trisomy 21 cells and atrioventricular canal malformations in down syndrome: A stochastic model. Am J Med Genet 1985;20:385–399.

    PubMed  CAS  Google Scholar 

  114. Jongewaard IN, Lauer RM, Behrendt DA et al. Beta 1 integrin activation mediates adhesive differences between trisomy 21 and nontrisomic fibroblasts on type VI collagen. Am J Med Genet 2002;109(4):298–305.

    PubMed  Google Scholar 

  115. Sheffield VC, Pierpont ME, Nishimura D et al. Identification of a complex congenital heart defect susceptibility locus by using DNA pooling and shared segment analysis. Hum Mol Genet 1997;6(1):117–121.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona, USA

    Raymond B. Runyan

  2. Department of Surgery, University of Arizona, Tucson, Arizona, USA

    Ronald L. Heimark

  3. Departments of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USA

    Todd D. Camenisch

  4. Department of Pediattics, University of Arizona, Tucson, Arizona, USA

    Scott E. Klewer

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  1. Raymond B. Runyan
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  4. Scott E. Klewer
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Runyan, R.B., Heimark, R.L., Camenisch, T.D., Klewer, S.E. (2005). Epithelial-Mesenchymal Transformation in the Embryonic Heart. In: Rise and Fall of Epithelial Phenotype. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-28671-3_4

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