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Anatomical Science International

Erschienen in:

01.09.2009 | Special Issue on Cardiovascular Development

Roles of TGFβ and BMP during valvulo–septal endocardial cushion formation

verfasst von: Toshiyuki Yamagishi, Katsumi Ando, Hiroaki Nakamura

Erschienen in: Anatomical Science International | Ausgabe 3/2009

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Abstract

The primordia of valves and the atrioventricular septum arise from endocardial cushion tissue that is formed in the outflow tract (OFT) and in the atrioventricular (AV) regions during cardiogenesis. Abnormal development of the endocardial cushion results in various congenital heart diseases. Endocardial epithelial–mesenchymal transformation (EMT) is a critical process in cushion tissue formation and is regulated by many factors, such as growth factors, intercellular signaling molecules, transcription factors, and extracellular matrices. A signal that is produced by the myocardium of the AV and OFT regions and transferred to the adjacent endocardium across the extracellular matrix mediates EMT. Studies in vitro and genetic analyses have shown that transforming growth factor β and bone morphogenetic protein play central roles in the regulation of EMT during cushion tissue formation.

Akhurst RJ, Lehnert SA, Faissner A, Duffie E (1990) TGF beta in murine morphogenetic processes: the early embryo and cardiogenesis. Development 108:645–656PubMed

Armstrong EJ, Bischoff J (2004) Heart valve development: endothelial cell signaling and differentiation. Circ Res 95:459–470PubMedCrossRef

Arthur HM, Ure J, Smith AJ, Renforth G, Wilson DI, Torsney E, Charlton R, Parums DV, Jowett T, Marchuk DA, Burn J, Diamond AG (2000) Endoglin, an ancillary TGFβ receptor, is required for extraembryonic angiogenesis and plays a key role in heart development. Dev Biol 217:42–53PubMedCrossRef

Barlow AJ, Francis-West PH (1997) Ectopic application of recombinant BMP-2 and BMP-4 can change patterning of developing chick facial primordia. Development 124:391–398PubMed

Barrallo-Gimeno A, Nieto MA (2005) The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132:3151–3161PubMedCrossRef

Bartram U, Molin DG, Wisse LJ, Mohamad A, Sanford LP, Doetschman T, Speer CP, Poelmann RE, Gittenberger-de Groot AC (2001) Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of looping, myocardialization, endocardial cushion differentiation, and apoptosis in TGF-β₂-knockout mice. Circulation 103:2745–2752PubMed

Bei M, Maas R (1998) FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development. Development 125:4325–4333PubMed

Beppu H, Kawabata M, Hamamoto T, Chytil A, Minowa O, Noda T, Miyazono K (2000) BMP type II receptor is required for gastrulation and early development of mouse embryos. Dev Biol 221:249–258PubMedCrossRef

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

Bourdeau A, Dumont DJ, Letarte M (1999) A murine model of hereditary hemorrhagic telangiectasia. J Clin Invest 104:1343–1351PubMedCrossRef

Boyer AS, Ayerinskas II, Vincent EB, McKinney LA, Weeks DL, Runyan RB (1999a) TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. Dev Biol 208:530–545PubMedCrossRef

Boyer AS, Erickson CP, Runyan RB (1999b) Epithelial-mesenchymal transformation in the embryonic heart is mediated through distinct pertussis toxin-sensitive and TGFβ signal transduction mechanisms. Dev Dyn 214:81–91PubMedCrossRef

Brown CB, Boyer AS, Runyan RB, Barnett JV (1996) Antibodies to the Type II TGFβ receptor block cell activation and migration during atrioventricular cushion transformation in the heart. Dev Biol 174:248–257PubMedCrossRef

Brown CB, Boyer AS, Runyan RB, Barnett JV (1999) Requirement of type III TGF-β receptor for endocardial cell transformation in the heart. Science 283:2080–2082PubMedCrossRef

Camenisch TD, Spicer AP, Brehm-Gibson T, Biesterfeldt J, Augustine ML, Calabro A Jr, Kubalak S, Klewer SE, McDonald JA (2000) Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. J Clin Invest 106:349–360PubMedCrossRef

Camenisch TD, Molin DG, Person A, Runyan RB, Gittenberger-de Groot AC, McDonald JA, Klewer SE (2002a) Temporal and distinct TGFβ ligand requirements during mouse and avian endocardial cushion morphogenesis. Dev Biol 248:170–181PubMedCrossRef

Camenisch TD, Schroeder JA, Bradley J, Klewer SE, McDonald JA (2002b) Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. Nat Med 8:850–855PubMed

Chang CP, Neilson JR, Bayle JH, Gestwicki JE, Kuo A, Stankunas K, Graef IA, Crabtree GR (2004) A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis. Cell 118:649–663PubMedCrossRef

Chan-Thomas PS, Thompson RP, Robert B, Yacoub MH, Barton PJ (1993) Expression of homeobox genes Msx-1 (Hox-7) and Msx-2 (Hox-8) during cardiac development in the chick. Dev Dyn 197:203–216PubMed

Chen Y, Bei M, Woo I, Satokata I, Maas R (1996) Msx1 controls inductive signaling in mammalian tooth morphogenesis. Development 122:3035–3044PubMed

Chen B, Bronson RT, Klaman LD, Hampton TG, Wang JF, Green PJ, Magnuson T, Douglas PS, Morgan JP, Neel BG (2000) Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat Genet 24:296–299PubMedCrossRef

Chen YH, Ishii M, Sun J, Sucov HM, Maxson RE Jr (2007) Msx1 and Msx2 regulate survival of secondary heart field precursors and post-migratory proliferation of cardiac neural crest in the outflow tract. Dev Biol 308:421–437PubMedCrossRef

Choudhary B, Ito Y, Makita T, Sasaki T, Chai Y, Sucov HM (2006). Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFbeta receptor (Tgfbr2) mutant mice. Dev Biol 289:420–429

De La Cruz MV, Sánchez-Gómez C, Palomino MA (1989) The primitive cardiac regions in the straight tube heart (Stage 9) and their anatomical expression in the mature heart: an experimental study in the chick embryo. J Anat 165:121–131PubMed

Délot EC, Bahamonde ME, Zhao M, Lyons KM (2003) BMP signaling is required for septation of the outflow tract of the mammalian heart. Development 130:209–220PubMedCrossRef

Desgrosellier JS, Mundell NA, McDonnell MA, Moses HL, Barnett JV (2005) Activin receptor-like kinase 2 and Smad6 regulate epithelial-mesenchymal transformation during cardiac valve formation. Dev Biol 280:201–210PubMedCrossRef

Dewulf N, Verschueren K, Lonnoy O, Morén A, Grimsby S, Vande Spiegle K, Miyazono K, Huylebroeck D, Ten Dijke P (1995) Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesis. Endocrinology 136:2652–2663PubMedCrossRef

Dickson MC, Slager HG, Duffie E, Mummery CL, Akhurst RJ (1993) RNA and protein localisations of TGFβ2 in the early mouse embryo suggest an involvement in cardiac development. Development 117:625–639PubMed

Dor Y, Camenisch TD, Itin A, Fishman GI, McDonald JA, Carmeliet P, Keshet E (2001) A novel role for VEGF in endocardial cushion formation and its potential contribution to congenital heart defects. Development 128:1531–1538PubMed

Ducy P, Karsenty G (2000) The family of bone morphogenetic proteins. Kidney Int 57:2207–2214PubMedCrossRef

Dudley AT, Robertson EJ (1997) Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Dev Dyn 208:349–362PubMedCrossRef

Erickson SL, O’Shea KS, Ghaboosi N, Loverro L, Frantz G, Bauer M, Lu LH, Moore MW (1997) ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. Development 124:4999–5011PubMed

Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9: 669–676

Fischer A, Steidl C, Wagner TU, Lang E, Jakob PM, Friedl P, Knobeloch KP, Gessler M (2007) Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition. Circ Res 100:856–863PubMedCrossRef

Flanders KC, Lüdecke G, Engels S, Cissel DS, Roberts AB, Kondaiah P, Lafyatis R, Sporn MB, Unsicker K (1991) Localization and actions of transforming growth factor-βs in the embryonic nervous system. Development 113:183–191PubMed

Galvin KM, Donovan MJ, Lynch CA, Meyer RI, Paul RJ, Lorenz JN, Fairchild-Huntress V, Dixon KL, Dunmore JH, Gimbrone MA Jr, Falb D, Huszar D (2000) A role for smad6 in development and homeostasis of the cardiovascular system. Nat Genet 24:171–174PubMedCrossRef

Gaussin V, Van de Putte T, Mishina Y, Hanks MC, Zwijsen A, Huylebroeck D, Behringer RR, Schneider MD (2002) Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3. Proc Natl Acad Sci USA 99:2878–2883PubMedCrossRef

Gu Z, Reynolds EM, Song J, Lei H, Feijen A, Yu L, He W, MacLaughlin DT, van den Eijnden-van Raaij J, Donahoe PK, Li E (1999) The type I serine/threonine kinase receptor ActRIA (ALK2) is required for gastrulation of the mouse embryo. Development 126:2551–2561PubMed

Hazama M, Aono A, Ueno N, Fujisawa Y (1995) Efficient expression of a heterodimer of bone morphogenetic protein subunits using a baculovirus expression system. Biochem Biophys Res Commun 209:859–866PubMedCrossRef

Heine U, Munoz EF, Flanders KC, Ellingsworth LR, Lam HY, Thompson NL, Roberts AB, Sporn MB (1987) Role of transforming growth factor-β in the development of the mouse embryo. J Cell Biol 105:2861–2876PubMedCrossRef

High FA, Epstein JA (2008) The multifaceted role of Notch in cardiac development and disease. Nat Rev Genet 9:49–61PubMedCrossRef

Hurlstone AF, Haramis AP, Wienholds E, Begthel H, Korving J, Van Eeden F, Cuppen E, Zivkovic D, Plasterk RH, Clevers H (2003) The Wnt/β-catenin pathway regulates cardiac valve formation. Nature 425:633–637PubMedCrossRef

Ishii M, Han J, Yen HY, Sucov HM, Chai Y, Maxson RE Jr (2005) Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest. Development 132:4937–4950PubMedCrossRef

Iwamoto R, Mekada E (2006) ErbB and HB-EGF signaling in heart development and function. Cell Struct Funct 31:1–14PubMedCrossRef

Iwamoto R, Yamazaki S, Asakura M, Takashima S, Hasuwa H, Miyado K, Adachi S, Kitakaze M, Hashimoto K, Raab G, Nanba D, Higashiyama S, Hori M, Klagsbrun M, Mekada E (2003) Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function. Proc Natl Acad Sci USA 100:3221–3226PubMedCrossRef

Jiao K, Kulessa H, Tompkins K, Zhou Y, Batts L, Baldwin HS, Hogan BL (2003) An essential role of Bmp4 in the atrioventricular septation of the mouse heart. Genes Dev 17:2362–2367PubMedCrossRef

Jiao K, Langworthy M, Batts L, Brown CB, Moses HL, Baldwin HS (2006) Tgfβ signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development. Development 133:4585–4593PubMedCrossRef

Jones CM, Lyons KM, Hogan BL (1991) Involvement of bone morphogenetic protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111:531–542PubMed

Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N, Groffen J (1995) Abnormal lung development and cleft palate in mice lacking TGF-β3 indicates defects of epithelial-mesenchymal interaction. Nat Genet 11:415–421PubMedCrossRef

Kaartinen V, Dudas M, Nagy A, Sridurongrit S, Lu MM, Epstein JA (2004) Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells. Development 131:3481–3490PubMedCrossRef

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

Kingsley DM (1994) The TGF-β superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev 8:133–146PubMedCrossRef

Koli K, Saharinen J, Hyytiäinen M, Penttinen C, Keski-Oja J (2001) Latency, activation, and binding proteins of TGF-β. Microsc Res Tech 52:354–362PubMedCrossRef

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

Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S (1993) Transforming growth factor β1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 90:770–774PubMedCrossRef

Lai YT, Beason KB, Brames GP, Desgrosellier JS, Cleggett MC, Shaw MV, Brown CB, Barnett JV (2000) Activin receptor-like kinase 2 can mediate atrioventricular cushion transformation. Dev Biol 222:1–11PubMedCrossRef

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

Larsson J, Goumans MJ, Sjöstrand LJ, van Rooijen MA, Ward D, Levéen P, Xu X, ten Dijke P, Mummery CL, Karlsson S (2001) Abnormal angiogenesis but intact hematopoietic potential in TGF-β type I receptor-deficient mice. EMBO J 20:1663–1673PubMedCrossRef

Lehnert SA, Akhurst RJ (1988) Embryonic expression pattern of TGF beta type-1 RNA suggests both paracrine and autocrine mechanisms of action. Development 104:263–273PubMed

Letterio JJ, Geiser AG, Kulkarni AB, Roche NS, Sporn MB, Roberts AB (1994) Maternal rescue of transforming growth factor-β1 null mice. Science 264:1936–1938PubMedCrossRef

Liebner S, Cattelino A, Gallini R, Rudini N, Iurlaro M, Piccolo S, Dejana E (2004) β-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J Cell Biol 166:359–367PubMedCrossRef

Liu W, Selever J, Wang D, Lu MF, Moses KA, Schwartz RJ, Martin JF (2004) Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. Proc Natl Acad Sci USA 30:4489–4494CrossRef

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

Lyons KM, Hogan BL, Robertson EJ (1995) Colocalization of BMP 7 and BMP 2 RNAs suggests that these factors cooperatively mediate tissue interactions during murine development. Mech Dev 50:71–83PubMedCrossRef

Ma L, Lu MF, Schwartz RJ, Martin JF (2005) Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development 132:5601–5611PubMedCrossRef

Mariano JM, Montuenga LM, Prentice MA, Cuttitta F, Jakowlew SB (1998) Concurrent and distinct transcription and translation of transforming growth factor-β type I and type II receptors in rodent embryogenesis. Int J Dev Biol 42:1125–1136PubMed

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

Markwald RR, Fitzharris TP, Manasek FJ (1977) Structural development of endocardial cushions. Am J Anat 148:85–119PubMedCrossRef

Mercado-Pimentel ME, Hubbard AD, Runyan RB (2007) Endoglin and Alk5 regulate epithelial-mesenchymal transformation during cardiac valve formation. Dev Biol 304:420–432PubMedCrossRef

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

Millan FA, Denhez F, Kondaiah P, Akhurst RJ (1991) Embryonic gene expression patterns of TGF β1, β2 and β3 suggest different developmental functions in vivo. Development 111:131–143PubMed

Miquerol L, Langille BL, Nagy A (2000) Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression. Development 127:3941–3946PubMed

Mishina Y, Suzuki A, Ueno N, Behringer RR (1995) Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes Dev 9:3027–3037PubMedCrossRef

Mishina Y, Crombie R, Bradley A, Behringer RR (1999) Multiple roles for activin-like kinase-2 signaling during mouse embryogenesis. Dev Biol 213:314–326PubMedCrossRef

Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K (2002) Two major Smad pathways in TGF-β superfamily signalling. Genes Cells 7:1191–1204PubMedCrossRef

Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16:251–263PubMedCrossRef

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

Molin DG, Bartram U, Van der Heiden K, Van Iperen L, Speer CP, Hierck BP, Poelmann RE, Gittenberger-de-Groot AC (2003) Expression patterns of Tgfβ1–3 associate with myocardialisation of the outflow tract and the development of the epicardium and the fibrous heart skeleton. Dev Dyn 227:431–444PubMedCrossRef

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

Nakajima Y, Mironov V, Yamagishi T, Nakamura H, Markwald RR (1997a) Expression of smooth muscle alpha-actin in mesenchymal cells during formation of avian endocardial cushion tissue: a role for transforming growth factor β3. Dev Dyn 209:296–309PubMedCrossRef

Nakajima Y, Miyazono K, Kato M, Takase M, Yamagishi T, Nakamura H (1997b) Extracellular fibrillar structure of latent TGFβ binding protein-1: role in TGFβ-dependent endothelial-mesenchymal transformation during endocardial cushion tissue formation in mouse embryonic heart. J Cell Biol 136:193–204PubMedCrossRef

Nakajima Y, Yamagishi T, Nakamura H, Markwald RR, Krug EL (1998) An autocrine function for transforming growth factor (TGF)-β3 in the transformation of atrioventricular canal endocardium into mesenchyme during chick heart development. Dev Biol 194:99–113PubMedCrossRef

Nakajima Y, Yamagishi T, Yoshimura K, Nomura M, Nakamura H (1999) Antisense oligodeoxynucleotide complementary to smooth muscle α-actin inhibits endothelial-mesenchymal transformation during chick cardiogenesis. Dev Dyn 216:489–498PubMedCrossRef

Nakajima Y, Yamagishi T, Hokari S, Nakamura H (2000) Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: roles of transforming growth factor (TGF)-β and bone morphogenetic protein (BMP). Anat Rec 258:119–127PubMedCrossRef

Niessen K, Karsan A (2008) Notch signaling in cardiac development. Circ Res 102:1169–1181PubMedCrossRef

Nishimatsu S, Thomsen GH (1998) Ventral mesoderm induction and patterning by bone morphogenetic protein heterodimers in Xenopus embryos. Mech Dev 74:75–88PubMedCrossRef

Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (2000) Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci USA 97:2626–2631PubMedCrossRef

Okagawa H, Markwald RR, Sugi Y (2007) Functional BMP receptor in endocardial cells is required in atrioventricular cushion mesenchymal cell formation in chick. Dev Biol 306:179–192PubMedCrossRef

Oshima M, Oshima H, Taketo MM (1996) TGF-β receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev Biol 179:297–302PubMedCrossRef

Pelton RW, Nomura S, Moses HL, Hogan BL (1989) Expression of transforming growth factor β2 RNA during murine embryogenesis. Development 106:759–767PubMed

Pelton RW, Dickinson ME, Moses HL, Hogan BL (1990) In situ hybridization analysis of TGFβ3 RNA expression during mouse development: comparative studies with TGFβ1 and β2. Development 110:609–620PubMed

Pelton RW, Saxena B, Jones M, Moses HL, Gold LI (1991) Immunohistochemical localization of TGFβ1, TGFβ2, and TGFβ3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J Cell Biol 115:1091–1105PubMedCrossRef

Person AD, Garriock RJ, Krieg PA, Runyan RB, Klewer SE (2005) Frzb modulates Wnt-9a-mediated β-catenin signaling during avian atrioventricular cardiac cushion development. Dev Biol 278:35–48PubMedCrossRef

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

Potts JD, Dagle JM, Walder JA, Weeks DL, Runyan RB (1991) Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor β3. Proc Natl Acad Sci USA 88:1516–1520PubMedCrossRef

Proetzel G, Pawlowski SA, Wiles MV, Yin M, Boivin GP, Howles PN, Ding J, Ferguson MW, Doetschman T (1995) Transforming growth factor-β3 is required for secondary palate fusion. Nat Genet 11:409–414PubMedCrossRef

Rivera-Feliciano J, Tabin CJ (2006) Bmp2 instructs cardiac progenitors to form the heart-valve-inducing field. Dev Biol 295:580–588PubMedCrossRef

Roelen BA, Lin HY, Knezevic V, Freund E, Mummery CL (1994) Expression of TGF-βs and their receptors during implantation and organogenesis of the mouse embryo. Dev Biol 166:716–728PubMedCrossRef

Roelen BA, van Rooijen MA, Mummery CL (1997) Expression of ALK-1, a type 1 serine/threonine kinase receptor, coincides with sites of vasculogenesis and angiogenesis in early mouse development. Dev Dyn 209:418–430PubMedCrossRef

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

Romano LA, Runyan RB (2000) Slug is an essential target of TGFβ2 signaling in the developing chicken heart. Dev Biol 223:91–102PubMedCrossRef

Sakabe M, Matsui H, Sakata H, Ando K, Yamagishi T, Nakajima Y (2005) Understanding heart development and congenital heart defects through developmental biology: a segmental approach. Congenit Anom 45:107–118CrossRef

Sakabe M, Ikeda K, Nakatani K, Kawada N, Imanaka-Yoshida K, Yoshida T, Yamagishi T, Nakajima Y (2006) Rho kinases regulate endothelial invasion and migration during valvuloseptal endocardial cushion tissue formation. Dev Dyn 235:94–104PubMedCrossRef

Sakabe M, Sakata H, Matsui S, Ikeda K, Yamagishi T, Nakajima Y (2008) ROCK1 expression is regulated by TGFβ3 and ALK2 together with BMP during valvuloseptal endocardial cushion formation. Anat Rec 291:845–857CrossRef

Sanford LP, Ormsby I, Gittenberger-de Groot AC, Sariola H, Friedman R, Boivin GP, Cardell EL, Doetschman T (1997) TGFβ2 knockout mice have multiple developmental defects that are non-overlapping with other TGFβ knockout phenotypes. Development 124:2659–2670PubMed

Satokata I, Maas R (1994) Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Nat Genet 6:348–356PubMedCrossRef

Schmierer B, Hill CS (2007) TGFβ-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol 8:970–982PubMedCrossRef

Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D, Annunziata N, Doetschman T (1992) Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. Nature 359:693–699PubMedCrossRef

Solloway MJ, Robertson EJ (1999) Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup. Development 126:1753–1768PubMed

Somi S, Buffing AA, Moorman AF, Van Den Hoff MJ (2004) Dynamic patterns of expression of BMP isoforms 2, 4, 5, 6, and 7 during chicken heart development. Anat Rec A Discov Mol Cell Evol Biol 279:636–651PubMedCrossRef

Song L, Fässler R, Mishina Y, Jiao K, Baldwin HS (2007) Essential functions of Alk3 during AV cushion morphogenesis in mouse embryonic hearts. Dev Biol 301:276–286PubMedCrossRef

Sorensen LK, Brooke BS, Li DY, Urness LD (2003) Loss of distinct arterial and venous boundaries in mice lacking endoglin, a vascular-specific TGFβ coreceptor. Dev Biol 261:235–250PubMedCrossRef

Stottmann RW, Choi M, Mishina Y, Meyers EN, Klingensmith J (2004) BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium. Development 131:2205–2218PubMedCrossRef

Sugi Y, Yamamura H, Okagawa H, Markwald RR (2004) Bone morphogenetic protein-2 can mediate myocardial regulation of atrioventricular cushion mesenchymal cell formation in mice. Dev Biol 269:505–518PubMedCrossRef

Suzuki A, Kaneko E, Maeda J, Ueno N (1997a) Mesoderm induction by BMP-4 and -7 heterodimers. Biochem Biophys Res Commun 232:153–156PubMedCrossRef

Suzuki A, Ueno N, Hemmati-Brivanlou A (1997b) Xenopus msx1 mediates epidermal induction and neural inhibition by BMP4. Development 124:3037–3044PubMed

Timmerman LA, Grego-Bessa J, Raya A, Bertrán E, Pérez-Pomares JM, Díez J, Aranda S, Palomo S, McCormick F, Izpisúa-Belmonte JC, de la Pompa JL (2004) Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 18:99–115PubMedCrossRef

Todorovic V, Frendewey D, Gutstein DE, Chen Y, Freyer L, Finnegan E, Liu F, Murphy A, Valenzuela D, Yancopoulos G, Rifkin DB (2007) Long form of latent TGF-β binding protein 1 (Ltbp1L) is essential for cardiac outflow tract septation and remodeling. Development 134:3723–3732PubMedCrossRef

Waldo K, Miyagawa-Tomita S, Kumiski D, Kirby ML (1998) Cardiac neural crest cells provide new insight into septation of the cardiac outflow tract: aortic sac to ventricular septal closure. Dev Biol 196:129–144PubMedCrossRef

Wall NA, Hogan BL (1995) Expression of bone morphogenetic protein-4 (BMP-4), bone morphogenetic protein-7 (BMP-7), fibroblast growth factor-8 (FGF-8) and sonic hedgehog (SHH) during branchial arch development in the chick. Mech Dev 53:383–392PubMedCrossRef

Wang J, Sridurongrit S, Dudas M, Thomas P, Nagy A, Schneider MD, Epstein JA, Kaartinen V (2005) Atrioventricular cushion transformation is mediated by ALK2 in the developing mouse heart. Dev Biol 286:299–310PubMedCrossRef

Wang J, Nagy A, Larsson J, Dudas M, Sucov HM, Kaartinen V (2006) Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects. BMC Dev Biol 6:51PubMedCrossRef

Watanabe Y, Le Douarin NM (1996) A role for BMP-4 in the development of subcutaneous cartilage. Mech Dev 57:69–78PubMedCrossRef

Winnier G, Blessing M, Labosky PA, Hogan BL (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9:2105–2116PubMedCrossRef

Yamada M, Szendro PI, Prokscha A, Schwartz RJ, Eichele G (1999) Evidence for a role of Smad6 in chick cardiac development. Dev Biol 215:48–61PubMedCrossRef

Yamagishi T, Nakajima Y, Miyazono K, Nakamura H (1999a) Bone morphogenetic protein-2 acts synergistically with transforming growth factor-β3 during endothelial-mesenchymal transformation in the developing chick heart. J Cell Physiol 180:35–45PubMedCrossRef

Yamagishi T, Nakajima Y, Nakamura H (1999b) Expression of TGFβ3 RNA during chick embryogenesis: a possible important role in cardiovascular development. Cell Tissue Res 298:85–93PubMedCrossRef

Yamagishi T, Nakajima Y, Nishimatsu S, Nohno T, Ando K, Nakamura H (2001) Expression of bone morphogenetic protein-5 gene during chick heart development: possible roles in valvuloseptal endocardial cushion formation. Anat Rec 264:313–316PubMedCrossRef

Yamagishi T, Nakajima Y, Ando K, Nakamura H (2005) Msx1 expression during chick heart development: possible role in endothelial-mesenchymal transformation during cushion tissue formation. In: Artman M, Benson DW, Srivastava D, Nakazawa M (eds) Cardiovascular development and congenital malformations. Blackwell Futura, Malden, pp 69–71CrossRef

Zhang H, Bradley A (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122:2977–2986PubMed

Zhao Z, Rivkees SA (2004) Rho-associated kinases play a role in endocardial cell differentiation and migration. Dev Biol 275:183–191PubMedCrossRef

Titel: Roles of TGFβ and BMP during valvulo–septal endocardial cushion formation
verfasst von: Toshiyuki Yamagishi
Katsumi Ando
Hiroaki Nakamura
Publikationsdatum: 01.09.2009
Verlag: Springer Japan
Erschienen in: Anatomical Science International / Ausgabe 3/2009
Print ISSN: 1447-6959
Elektronische ISSN: 1447-073X
DOI: https://doi.org/10.1007/s12565-009-0027-0

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