Notch signaling in cardiac development

Circulation Research

Volumn 102, Issue 10, 2008, Pages 1169-1181

  Niessen, Kyle ^a,b   Karsan, Aly ^a,b,c  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c BRITISH COLUMBIA CANCER RESEARCH CENTRE   (Canada)

Author keywords

Angiogenesis; Cardiac development; Endothelial mesenchymal transformation; Notch; Vasculogenesis

Indexed keywords

BIOLOGICAL MARKER; BONE MORPHOGENETIC PROTEIN 2; EPHRIN B2; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 4; GELATINASE A; JAGGED1; MEMBRANE PROTEIN; NEU DIFFERENTIATION FACTOR; NOTCH RECEPTOR; NOTCH1 RECEPTOR; NOTCH2 RECEPTOR; NOTCH4 RECEPTOR; PROTEIN JAGGED2; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR HES 1; TRANSCRIPTION FACTOR HES 2; TRANSCRIPTION FACTOR SLUG; TRANSCRIPTION FACTOR SNAIL; TRANSCRIPTION FACTOR TBX2; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA2; UNCLASSIFIED DRUG; VASCULAR ENDOTHELIAL CADHERIN; VASCULOTROPIN;

ALAGILLE SYNDROME; ALLELE; AORTA VALVE DISEASE; ARTERY CALCIFICATION; ATRIOVENTRICULAR CANAL; BICUSPID AORTIC VALVE; CELL DIFFERENTIATION; CELL INTERACTION; CELL JUNCTION; CELL TRANSFORMATION; CONGENITAL HEART MALFORMATION; ENDOCARDIUM; FALLOT TETRALOGY; GENE EXPRESSION REGULATION; GENE MUTATION; GENE OVEREXPRESSION; GENE TARGETING; HEART ATRIUM; HEART DEVELOPMENT; HEART LEFT VENTRICLE OUTFLOW TRACT; HEART MUSCLE; HEART RIGHT VENTRICLE OUTFLOW TRACT; HEART VENTRICLE; HEART VENTRICLE FUNCTION; HUMAN; IN VIVO CULTURE; MOLECULAR INTERACTION; MUTANT; NEGATIVE FEEDBACK; NEURAL CREST CELL; NEWBORN JAUNDICE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PULMONARY VALVE STENOSIS; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; GENETICS; HEART; METABOLISM; PHYSIOLOGY; PRENATAL DEVELOPMENT;

ANIMALS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HEART; HUMANS; RECEPTORS, NOTCH; SIGNAL TRANSDUCTION;

EID: 45149102678     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.108.174318     Document Type: Review

References (129)

1. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coli Cardiol. 2002;39:1890-1900.
2. Ausoni S, Sartore S. Cell lineages and tissue boundaries in cardiac arterial and venous poles: developmental patterns, animal models, and implications for congenital vascular diseases. Arterioscler Thromb Vasc Biol. 2001;21:312-320.
3. Brand T. Heart development: molecular insights into cardiac specification and early morphogenesis. Dev Biol. 2003;258:1-19.
4. Kelly RG, Brown NA, Buckingham ME. The arterial pole of the mouse heart forms from Fgf 10-expressing cells in pharyngeal mesoderm. Dev Cell. 2001;1:435-440.
5. Jiang X, Rowitch DH, Soriano P, McMahon AP, Sucov HM. Fate of the mammalian cardiac neural crest. Development. 2000;127:1607-1616.
6. Komiyama M, Ito K, Shimada Y. Origin and development of the epi-cardium in the mouse embryo. Anat Embryol (Bed). 1987; 176:183-189.
7. Viragh S, Challice CE. The origin of the epicardium and the embryonic myocardial circulation in the mouse. Anat Rec. 1981;201:157-168.
8. Vrancken Peeters MP, Gittenberger-de Groot AC, Mentink MM, Poelmann RE. Smooth muscle cells and fibroblasts of the coronary arteries derive from epithelial-mesenchymal transformation of the epicardium. Anat Embryol (Bed). 1999;199:367-378.
9. Dettman RW, Denetclaw W Jr, Ordahl CP, Bristow J. Common epi-cardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol. 1998;193:169-181.
10. Taber LA. Mechanical aspects of cardiac development. Prog Biophys Mol Biol. 1998;69:237-255.
11. Keller BB, Liu LJ, Tinney JP, Tobita K. Cardiovascular developmental insights from embryos. Ann N Y Acad Sci. 2007;1101:377-388.
12. Person AD, Klewer SE, Runyan RB. Cell biology of cardiac cushion development. Int Rev Cytol. 2005;243:287-335.
13. Armstrong EJ, Bischoff J. Heart valve development: endothelial cell signaling and differentiation. Circ Res. 2004;95:459-470.
14. Srivastava D. Building a heart: implications for congenital heart disease. J Nucl Cardiol. 2003;10:1063-1070.
15. Fleming RJ. Structural conservation of Notch receptors and ligands. Semin Cell Dev Biol. 1998;9:599-607.
16. Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell. 1997;90:281-291.
17. Bush G, diSibio G, Miyamoto A, Denault JB, Leduc R, Weinmaster G. Ligand-induced signaling in the absence of furin processing of Notchl. Dev Biol. 2001;229:494-502.
18. Huppert SS, Jacobsen TL, Muskavitch MA. Feedback regulation is central to Delta-Notch signalling required for Drosophila wing vein morphogenesis. Development. 1997;124:3283-3291.
19. Seugnet L, Simpson P, Haenlin M. Transcriptional regulation of Notch and Delta: requirement for neuroblast segregation in Drosophila. Development. 1997; 124:2015-2025.
20. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284: 770-776.
21. Pedrazzini T. Control of cardiogenesis by the notch pathway. Trends Cardiovasc Med. 2007;17:83-90.
22. Glittenberg M, Pitsouli C, Garvey C, Delidakis C, Bray S. Role of conserved intracellular motifs in Serrate signalling, cis-inhibition and endocytosis. EMBO J. 2006;25:4697-4706.
23. Li Y, Baker NE. The roles of cis-inactivation by Notch ligands and of neuralized during eye and bristle patterning in Drosophila. BMC Dev Biol. 2004;4:5.
24. Haines N, Irvine KD. Glycosylation regulates Notch signalling. Nat Rev Mol Cell Biol. 2003;4:786-797.
25. Moloney DJ, Shair LH, Lu FM, Xia J, Locke R, Matta KL, Haltiwanger RS. Mammalian Notchl is modified with two unusual forms of O-linked glycosylation found on epidermal growth factor-like modules. J Biol Chem. 2000;275:9604-9611.
26. Munro S, Freeman M. The notch signalling regulator fringe acts in the Golgi apparatus and requires the glycosyltransferase signature motif DXD. Curr Biol. 2000;10:813-820.
27. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 1999;398:518-522.
28. Strahl G, Greenwald I. Presenilin-mediated transmembrane cleavage is required for Notch signal transduction in Drosophila. Proc Natl Acad Sci U S A. 2001;98:229-234.
29. Hu Y, Ye Y, Fortini ME. Nicastrin is required for gamma-secretase cleavage of the Drosophila Notch receptor. Dev Cell. 2002;2:69-78.
30. Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, Nicoll M, Maxwell M, Hai B, Ellis MC, Parks AL, Xu W, Li J, Gurney M, Myers RL, Himes CS, Hiebsch R, Ruble C, Nye JS, Curtis D. aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell. 2002;3:85-97.
31. Okochi M, Steiner H, Fukumori A, Tanii H, Tomita T, Tanaka T, Iwatsubo T, Kudo T, Takeda M, Haass C. Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1. EMBO J. 2002;21:5408-5416.
32. Hiratochi M, Nagase H, Kuramochi Y, Koh CS, Ohkawara T, Nakayama K. The Delta intracellular domain mediates TGF-{beta}/Activin signaling through binding to Smads and has an important bi-directional function in the Notch-Delta signaling pathway. Nucleic Acids Res. 2007;35:912-922.
33. Tamura K, Taniguchi Y, Minoguchi S, Sakai T, Tun T, Furukawa T, Honjo T. Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H). Curr Biol. 1995; 5:1416-1423.
34. Davis RL, Turner DL. Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning. Oncogene. 2001;20:8342-8357.
35. Iso T, Chung G, Hamamori Y, Kedes L. HERP1 is a cell type-specific primary target of Notch. J Biol Chem. 2002;277:6598-6607.
36. Ge W, Martinowich K, Wu X, He F, Miyamoto A, Fan G, Weinmaster G, Sun YE. Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene activation. J Neurosci Res. 2002;69:848-860.
37. Klinakis A, Szabolcs M, Politi K, Kiaris H, Artavanis-Tsakonas S, Efstratiadis A. Myc is a Notchl transcriptional target and a requisite for Notchl-induced mammary tumorigenesis in mice. Proc Natl Acad Sci U S A. 2006; 103:9262-9267.
38. Krebs LT, Iwai N, Nonaka S, Welsh IC, Lan Y, Jiang R, Saijoh Y, O'Brien TP, Hamada H, Gridley T. Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev. 2003;17:1207-1212.
39. Noseda M, Fu Y, Niessen K, Wong F, Chang L, McLean G, Karsan A. Smooth muscle {alpha}-actin is a direct target of Notch/CSL. Circ Res. 2006;98:1468-1470.
40. Rangarajan A, Talora C, Okuyama R, Nicolas M, Mammucari C, Oh H, Aster JC, Krishna S, Metzger D, Chambon P, Miele L, Aguet M, Radtke F, Dotto GP. Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J. 2001;20: 3427-3436.
41. Ronchini C, Capobianco AJ. Induction of cyclin Dl transcription and CDK2 activity by Notch(ic): implication for cell cycle disruption in transformation by Notch(ic). Mol Cell Biol. 2001;21:5925-5934.
42. Whelan JT, Forbes SL, Bertrand FE. CBF-1 (RBP-Jkappa) binds to the PTEN promoter and regulates PTEN gene expression. Cell Cycle. 2007; 6:80-84.
43. Grego-Bessa J, Luna-Zurita L, Del Monte G, Bolos V, Melgar P, Arandilla A, Garratt AN, Zang H, Mukouyama YS, Chen H, Shou W, Ballestar E, Esteller M, Rojas A, Perez-Pomares JM, de la Pompa JL. Notch signaling is essential for ventricular chamber development. Dev Cell. 2007;12:415-429.
44. Iso T, Maeno T, Oike Y, Yamazaki M, Doi H, Arai M, Kurabayashi M. D114-selective Notch signaling induces ephrinB2 gene expression in endothelial cells. Biochem Biophys Res Commun. 2006;341:708-714.
45. Martinez Arias A, Zecchini V, Brennan K. CSL-independent Notch signalling: a checkpoint in cell fate decisions during development? Curr Opin Genet Dev. 2002;12:524-533.
46. Fiuza UM, Arias AM. Cell and molecular biology of Notch. J Endocrinol. 2007;194:459-474.
47. Leong KG, Karsan A. Recent insights into the role of Notch signaling in tumorigenesis. Blood. 2006;107:2223-2233.
48. Hofmann JJ, Iruela-Arispe ML. Notch signaling in blood vessels: who is talking to whom about what? Circ Res. 2007;100:1556-1568.
49. Karsan A. The role of notch in modeling and maintaining the vasculature. Can J Physiol Pharmacol. 2005;83:14-23.
50. Souilhol C, Cormier S, Tanigaki K, Babinet C, Cohen-Tannoudji M. RBP-Jkappa-dependent notch signaling is dispensable for mouse early embryonic development. Mol Cell Biol. 2006;26:4769-4774.
51. Przemeck GK, Heinzmann U, Beckers J, Hrabe de Angelis M. Node and midline defects are associated with left-right development in Deltal mutant embryos. Development. 2003;130:3-13.
52. Han Z, Bodmer R. Myogenic cells fates are antagonized by Notch only in asymmetric lineages of the Drosophila heart, with or without cell division. Development. 2003;130:3039-3051.
53. Rones MS, McLaughlin KA, Raffln M, Mercola M. Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis. Development. 2000;127:3865-3876.
54. Schroeder T, Fraser ST, Ogawa M, Nishikawa S, Oka C, Bornkamm GW, Nishikawa S, Honjo T, Just U. Recombination signal sequence-binding protein Jkappa alters mesodermal cell fate decisions by suppressing cardiomyogenesis. Proc Natl Acad Sci U S A. 2003;100:4018-4023.
55. Eisenberg LM, Markwald RR. Molecular regulation of atrioventricular valvuloseptal morphogenesis. Circ Res. 1995;77:1-6.
56. van Kempen MJ, Fromaget C, Gros D, Moorman AF, Lamers WH. Spatial distribution of connexin43, the major cardiac gap junction protein, in the developing and adult rat heart. Circ Res. 1991;68:1638-1651.
57. Zhang H, Bradley A. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development. 1996;122:2977-2986.
58. Harrelson Z, Kelly RG, Goldin SN, Gibson-Brown JJ, Bollag RJ, Silver LM, Papaioannou VE. Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development. Development. 2004; 131:5041-5052.
59. Ma L, Lu MF, Schwartz RJ, Martin JF. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development. 2005;132:5601-5611.
60. Yamada M, Revelli JP, Eichele G, Barron M, Schwartz RJ. Expression of chick Tbx-2, Tbx-3, and Tbx-5 genes during early heart development: evidence for BMP2 induction of Tbx2. Dev Biol. 2000;228:95-105.
61. Fischer A, Steidl C, Wagner TU, Lang E, Jakob PM, Friedl P, Kno-beloch KP, Gessier M. Combined loss of Heyl and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition. Circ Res. 2007;100:856-863.
62. McCright B, Gao X, Shen L, Lozier J, Lan Y, Maguire M, Herzlinger D, Weinmaster G, Jiang R, Gridley T. Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypo-morphic Notch2 mutation. Development. 2001;128:491-502.
63. Xue Y, Gao X, Lindsell CE, Norton CR, Chang B, Hicks C, Gendron-Maguire M, Rand EB, Weinmaster G, Gridley T. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jaggedl. Hum Mol Genet. 1999;8:723-730.
64. Sakata Y, Kamei CN, Nakagami H, Bronson R, Liao JK, Chin MT. Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2. Proc Natl Acad Sci U S A. 2002;99: 16197-16202.
65. Gessler M, Knobeloch KP, Helisch A, Amann K, Schumacher N, Rohde E, Fischer A, Leimeister C. Mouse gridlock: no aortic coarctation or deficiency, but fatal cardiac defects in Hey2-/- mice. Curr Biol. 2002;12:1601-1604.
66. Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M. The Notch target genes Hey 1 and Hey2 are required for embryonic vascular development. Genes Dev. 2004; 18:901-911.
67. Oka C, Nakano T, Wakeham A, de la Pompa JL, Mori C, Sakai T, Okazaki S, Kawaichi M, Shiota K, Mak TW, Honjo T. Disruption of the mouse RBP-J kappa gene results in early embryonic death. Development. 1995; 121:3291-3301.
68. Watanabe Y, Kokubo H, Miyagawa-Tomita S, Endo M, Igarashi K, Aisaki KI, Kanno J, Saga Y. Activation of Notchl signaling in car-diogenic mesoderm induces abnormal heart morphogenesis in mouse. Development. 2006; 133:1625-1634.
69. Rutenberg JB, Fischer A, Jia H, Gessler M, Zhong TP, Mercola M. Developmental patterning of the cardiac atrioventricular canal by Notch and Hairy-related transcription factors. Development. 2006;133: 4381-4390.
70. Kokubo H, Tomita-Miyagawa S, Hamada Y, Saga Y. Hesrl and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2. Development. 2007;134:747-755.
71. Leimeister C, Externbrink A, Klamt B, Gessler M. Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis. Mech Dev. 1999;85:173-177.
72. Loomes KM, Underkoffler LA, Morabito J, Gottlieb S, Piccoli DA, Spinner NB, Baldwin HS, Oakey RJ. The expression of Jaggedl in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome. Hum Mol Genet. 1999;8:2443-2449.
73. Hamada Y, Kadokawa Y, Okabe M, Ikawa M, Coleman JR, Tsujimoto Y. Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development. 1999;126:3415-3424.
74. Loomes KM, Taichman DB, Glover CL, Williams PT, Markowitz JE, Piccoli DA, Baldwin HS, Oakey RJ. Characterization of Notch receptor expression in the developing mammalian heart and liver. Am J Med Genet. 2002;112:181-189.
75. Donovan J, Kordylewska A, Jan YN, Utset MF. Tetralogy of Fallot and other congenital heart defects in Hey2 mutant mice. Curr Biol. 2002; 12:1605-1610.
76. Kokubo H, Miyagawa-Tomita S, Tomimatsu H, Nakashima Y, Nakazawa M, Saga Y, Johnson RL. Targeted disruption of hesr2 results in atrioventricular valve anomalies that lead to heart dysfunction. Circ Res. 2004;95:540-547.
77. Saga Y, Miyagawa-Tomita S, Takagi A, Kitajima S, Miyazaki J, Inoue T. MesPl is expressed in the heart precursor cells and required for the formation of a single heart tube. Development. 1999;126:3437-3447.
78. Saga Y, Kitajima S, Miyagawa-Tomita S. Mespl expression is the earliest sign of cardiovascular development. Trends Cardiovasc Med. 2000; 10:345-352.
79. Singh MK, Christoffels VM, Dias JM, Trowe MO, Petty M, Schuster-Gossler K, Burger A, Ericson J, Kispert A. Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2. Development. 2005; 132:2697-2707.
80. Benedito R, Duarte A. Expression of D114 during mouse embryogenesis suggests multiple developmental roles. Gene Expr Patterns. 2005;5: 750-755.
81. Del Monte G, Grego-Bessa J, Gonzalez-Rajal A, Bolos V, De La Pompa JL. Monitoring Notchl activity in development: evidence for a feedback regulatory loop. Dev Dyn. 2007;236:2594-2614.
82. Timmerman LA, Grego-Bessa J, Raya A, Bertran E, Perez-Pomares JM, Diez J, Aranda S, Palomo S, McCormick F, rzpisua-Belmonte JC, de la Pompa JL. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004;18: 99-115.
83. Song W, Jackson K, McGuire PG. Degradation of type IV collagen by matrix metalloproteinases is an important step in the epithelial-mesenchymal transformation of the endocardial cushions. Dev Biol. 2000;227:606-617.
84. Crosby CV, Fleming PA, Argraves WS, Corada M, Zanetta L, Dejana E, Drake CJ. VE-cadherin is not required for the formation of nascent blood vessels but acts to prevent their disassembly. Blood. 2005;105: 2771-2776.
85. Messen K, Fu Y, Chang L, Hoodless PA, McFadden D, Karsan A. Slug is a direct Notch target required for initiation of cardiac cushion cellu-larization. J Cell Biol. In press.
86. Miquerol L, Gertsenstein M, Harpal K, Rossant J, Nagy A. Multiple developmental roles of VEGF suggested by a LacZ-tagged allele. Dev Biol. 1999;212:307-322.
87. Miquerol L, Languie BL, Nagy A. Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression. Development. 2000;127:3941-3946.
88. Dor Y, Camenisch TD, Itin A, Fishman GI, McDonald JA, Carmeliet P, Keshet E. A novel role for VEGF in endocardial cushion formation and its potential contribution to congenital heart defects. Development. 2001; 128:1531-1538.
89. Noseda M, McLean G, Messen K, Chang L, Pollet I, Montpetit R, Shahidi R, Dorovini-Zis K, Li L, Beckstead B, Durand RE, Hoodless PA, Karsan A. Notch activation results in phenotypic and functional changes consistent with endothelial-to-mesenchymal transformation. Circ Res. 2004;94:910-917.
90. Lobov IB, Renard RA, Papadopoulos N, Gale NW, Thurston G, Yan-copoulos GD, Wiegand SJ. Delta-like ligand 4 (D114) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc Natl Acad Sci U S A. 2007;104:3219-3224.
91. Liu ZJ, Shirakawa T, Li Y, Soma A, Oka M, Dotto GP, Fairman RM, Velazquez OC, Herlyn M. Regulation of Notchl and D114 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis. Mol Cell Biol. 2003;23:14-25.
92. van den Akker NM, Molin DG, Peters PP, Maas S, Wisse LJ, van Brempt R, van Munsteren CJ, Bartelings MM, Poelmann RE, Carmeliet P, Gittenberger-de Groot AC. Tetralogy of fallot and alterations in vascular endothelial growth factor-A signaling and notch signaling in mouse embryos solely expressing the VEGF 120 isoform. Circ Res. 2007;100:842-849.
93. Moorman AF, Christoffels VM. Cardiac chamber formation: development, genes, and evolution. Physiol Rev. 2003;83:1223-1267.
94. Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. Nature. 1995;378:386-390.
95. Erickson SL, O'Shea KS, Ghaboosi N, Loverro L, Frantz G, Bauer M, Lu LH, Moore MW. ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. Development. 1997;124:4999-5011.
96. Gassmann M, Casagranda F, Orioli D, Simon H, Lai C, Klein R, Lemke G. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature. 1995;378:390-394.
97. Chen H, Shi S, Acosta L, Li W, Lu J, Bao S, Chen Z, Yang Z, Schneider MD, Chien KR, Conway SJ, Yoder MC, Haneline LS, Franco D, Shou W. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development. 2004;131:2219-2231.
98. Gerety SS, Wang HU, Chen ZF, Anderson DJ. Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol Cell. 1999;4:403-414.
99. Wang J, Sridurongrit S, Dudas M, Thomas P, Nagy A, Schneider MD, Epstein JA, Kaartinen V. Atrioventricular cushion transformation is mediated by ALK2 in the developing mouse heart. Dev Biol. 2005;286: 299-310.
100. Villa N, Walker L, Lindsell CE, Gasson J, Iruela-Arispe ML, Wein-master G. Vascular expression of Notch pathway receptors and ligands is restricted to arterial vessels. Mech Dev. 2001;108:161-164.
101. Koibuchi N, Chin MT. CHF1/Hey2 plays a pivotal role in left ventricular maturation through suppression of ectopic atrial gene expression. Circ Res. 2007;10:850-855.
102. Xin M, Small EM, van Rooij E, Qi X, Richardson JA, Srivastava D, Nakagawa O, Olson EN. Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function. Proc Natl Acad Sci U S A. 2007;104:7975-7980.
103. Asahi M, Otsu K, Nakayama H, Hikoso S, Takeda T, Gramolini AO, Trivieri MG, Oudit GY, Morita T, Kusakari Y, Hirano S, Hongo K, Hirotani S, Yamaguchi O, Peterson A, Backx PH, Kurihara S, Hori M, MacLennan DH. Cardiac-specific overexpression of sarcolipin inhibits sar-co(endo)plasmic reticulum Ca2 + ATPase (SERCA2a) activity and impairs cardiac function in mice. Proc Natl Acad Sci U S A. 2004;101:9199-9204.
104. Restivo A, Piacentini G, Placidi S, Saffirio C, Marino B. Cardiac outflow tract: a review of some embryogenetic aspects of the conotruncal region of the heart. Anat Rec A Discov Mol Cell Evol Biol. 2006;288:936-943.
105. Charron F, Paradis P, Bronchain O, Nemer G, Nemer M. Cooperative interaction between GATA-4 and GATA-6 regulates myocardial gene expression. Mol Cell Biol. 1999;19:4355-4365.
106. Fischer A, Klattig J, Kneitz B, Diez H, Maier M, Holtmann B, Englert C, Gessler M. Hey basic helix-loop-helix transcription factors are repressors of GATA4 and GATA6 and restrict expression of the GATA target gene ANF in fetal hearts. Mol Cell Biol. 2005;25:8960-8970.
107. Anderson RH, Webb S, Brown NA, Lamers W, Moorman A. Development of the heart: (3) formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks. Heart. 2003;89:1110-1118.
108. de Lange FJ, Moorman AF, Anderson RH, Manner J, Soufan AT, de Gier-de Vries C, Schneider MD, Webb S, van den Hoff MJ, Christoffels VM. Lineage and morphogenetic analysis of the cardiac valves. Circ Res. 2004;95:645-654.
109. Kaartinen V, Dudas M, Nagy A, Sridurongrit S, Lu MM, Epstein JA. Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells. Development. 2004; 131:3481-3490.
110. Kim RY, Robertson EJ, Solloway MJ. Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Dev Biol. 2001;235:449-466.
111. Jiao K, Kulessa H, Tompkins K, Zhou Y, Batts L, Baldwin HS, Hogan BL. An essential role of Bmp4 in the atrioventricular septation of the mouse heart. Genes Dev. 2003;17:2362-2367.
112. High FA, Zhang M, Proweller A, Tu L, Parmacek MS, Pear WS, Epstein JA. An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest. 2007; 117:353-363.
113. Proweller A, Pear WS, Parmacek MS. Notch signaling represses myocardin-induced smooth muscle cell differentiation. J Biol Chem. 2005;280:8994-9004.
114. Doi H, Iso T, Sato H, Yamazaki M, Matsui H, Tanaka T, Manabe I, Arai M, Nagai R, Kurabayashi M. Jaggedl-selective notch signaling induces smooth muscle differentiation via a RBP-Jkappa-dependent pathway. J Biol Chem. 2006;281:28555-28564.
115. Doi H, Iso T, Yamazaki M, Akiyama H, Kanai H, Sato H, Kawai-Kowase K, Tanaka T, Maeno T, Okamoto E, Arai M, Kedes L, Kurabayashi M. HERP1 inhibits myocardin-induced vascular smooth muscle cell differentiation by interfering with SRF binding to CArG box. Arterioscler Thromb Vasc Biol. 2005;25:2328-2334.
116. Maillard I, Weng AP, Carpenter AC, Rodriguez CG, Sai H, Xu L, Allman D, Aster JC, Pear WS. Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood. 2004;104:1696-1702.
117. Tu L, Fang TC, Artis D, Shestova O, Pross SE, Maillard I, Pear WS. Notch signaling is an important regulator of type 2 immunity. J Exp Med. 2005;202:1037-1042.
118. Shen H, McElhinny AS, Cao Y, Gao P, Liu J, Bronson R, Griffin JD, Wu L. The Notch coactivator, MAML1, functions as a novel coactivator for MEF2C-mediated transcription and is required for normal myogenesis. Genes Dev. 2006;20:675-688.
119. Zhao Y, Katzman RB, Delmolino LM, Bhat I, Zhang Y, Gurumurthy CB, Germaniuk-Kurowska A, Reddi HV, Solomon A, Zeng MS, Kung A, Ma H, Gao Q, Dimri G, Stanculescu A, Miele L, Wu L, Griffin JD, Wazer DE, Band H, Band V. The notch regulator MAML1 interacts with p53 and functions as a coactivator. J Biol Chem. 2007;282: 11969-11981.
120. Warthen DM, Moore EC, Kamath BM, Morrissette JJ, Sanchez P, Piccoli DA, Krantz ID, Spinner NB. Jaggedl (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat. 2006;27:436-443.
121. McDaniell R, Warthen DM, Sanchez-Lara PA, Pai A, Krantz ID, Piccoli DA, Spinner NB. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet. 2006;79:169-173.
122. Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, Krantz ID. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004;109:1354-1358.
123. McElhinney DB, Krantz ID, Bason L, Piccoli DA, Emerick KM, Spinner NB, Goldmuntz E. Analysis of cardiovascular phenotype and genotype-phenotype correlation in individuals with a JAG1 mutation and/or Alagille syndrome. Circulation. 2002;106:2567-2574.
124. Krantz ID, Smith R, Colliton RP, Tinkel H, Zackai EH, Piccoli DA, Goldmuntz E, Spinner NB. Jaggedl mutations in patients ascertained with isolated congenital heart defects. Am J Med Genet. 1999;84:56-60.
125. Spinner NB, Colliton RP, Crosnier C, Krantz ID, Hadchouel M, Meunier-Rotival M. Jaggedl mutations in alagille syndrome. Hum Mutat. 2001;17:18-33.
126. McCright B, Lozier J, Gridley T. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jagl haploinsufficiency. Development. 2002;129:1075-1082.
127. High FA, Lu MM, Pear WS, Loomes KM, Kaestner KH, Epstein JA. Endothelial expression of the Notch ligand Jaggedl is required for vascular smooth muscle development. Proc Natl Acad Sci U S A. 2008; 105:1955-1959.
128. Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD, Srivastava D. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005;437:270-274.
129. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfal: a transcriptional activator of osteoblast differentiation. Cell. 1997;89: 747-754.