T-box factors: Insights into the evolutionary emergence of the complex heart

Annals of Medicine

Volumn 44, Issue 7, 2012, Pages 680-693

  Hariri, Fadi ^a,b   Nemer, Mona ^c   Nemer, Georges ^b  

^a INSTITUTE FOR RESEARCH IN IMMUNOLOGY AND CANCER   (Canada)

^b AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

^c UNIVERSITY OF OTTAWA   (Canada)

Author keywords

Congenital heart disease; Evolution; Heart development; T box genes

Indexed keywords

BETA CATENIN; CELL ADHESION MOLECULE; HISTONE DEACETYLASE 1; MYOSIN HEAVY CHAIN; NERVE CELL ADHESION MOLECULE; PALINDROMIC DNA; REGULATOR PROTEIN; RETINOIC ACID; SMAD PROTEIN; T BOX TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GATA 4; TRANSCRIPTION FACTOR NKX2.5; TRANSCRIPTION FACTOR TBX5; ZINC FINGER PROTEIN;

AORTA ARCH ANOMALY; ATRIOVENTRICULAR CANAL; BLOOD CELL; BLOOD VESSEL; CARDIOVASCULAR SYSTEM; CELL GROWTH; CONGENITAL HEART MALFORMATION; DIGEORGE SYNDROME; DNA BINDING; FIBROBLAST; GENE DOSAGE; GENE DUPLICATION; GENE TARGETING; GREAT VESSELS TRANSPOSITION; HAPLOINSUFFICIENCY; HEART DEVELOPMENT; HEART LEFT VENTRICLE; HEART MUSCLE; HEART MUSCLE CELL; HEART MUSCLE CONDUCTION SYSTEM; HEART RIGHT VENTRICLE; HEART VENTRICLE SEPTUM; HEART VENTRICLE SEPTUM DEFECT; HUMAN; HYPOPLASTIC LEFT HEART SYNDROME; MESODERM; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PULMONARY VALVE ATRESIA; PULMONARY VALVE STENOSIS; REGULATORY MECHANISM; REVIEW; SINUS NODE; SINUS VENOSUS; SMOOTH MUSCLE; SYSTEMIC CIRCULATION; WNT SIGNALING PATHWAY;

ANIMALS; BIOLOGICAL EVOLUTION; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HEART; HEART CONDUCTION SYSTEM; HEART DEFECTS, CONGENITAL; HUMANS; MYOCARDIUM; T-BOX DOMAIN PROTEINS;

EID: 84868232567     PISSN: 07853890     EISSN: 13652060     Source Type: Journal    
DOI: 10.3109/07853890.2011.607468     Document Type: Review

References (116)

1. Nemer G, Nemer M. Regulation of heart development and function through combinatorial interactions of transcription factors. Ann Med. 2001;33:604-10.
2. Gruber PJ. Cardiac development: new concepts. Clin Perinatol. 2005;32:845-55, vii.
3. Brand T. Heart development: molecular insights into cardiac specifi cation and early morphogenesis. Dev Biol. 2003;258: 1-19.
4. Buckingham M, Meilhac S, Zaffran S. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet. 2005;6:826-35.
5. Hoogaars WM, Barnett P, Moorman AF, Christoffels VM. T-box factors determine cardiac design. Cell Mol Life Sci. 2007;64:646-60.
6. Gilbert SF. Lateral plate mesoderm and endoderm. Developmental biology. 6th ed. Sinauer Associates, Inc., Publishers, Sunderland, MA, USA.
7. Olson EN. Gene regulatory networks in the evolution and development of the heart. Science. 2006;313:1922-7.
8. Lints TJ, Parsons LM, Hartley L, Lyons I, Harvey RP. Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development. 1993;119:419-31.
9. Heikinheimo M, Scandrett JM, Wilson DB. Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac development. Dev Biol. 1994;164:361-73.
10. Molkentin JD, Kalvakolanu DV, Markham BE. Transcription factor GATA-4 regulates cardiac muscle-specifi c expression of the alpha-myosin heavy-chain gene. Mol Cell Biol. 1994;14:4947-57.
11. Bruneau BG, Logan M, Davis N, Levi T, Tabin CJ, Seidman JG, et al. Chamber-specifi c cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. Dev Biol. 1999;211:100-8.
12. Zaffran S, Frasch M. Early signals in cardiac development. Circ Res. 2002;91:457-69.
13. Schultheiss TM, Burch JB, Lassar AB. A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev. 1997;11:451-62.
14. Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature. 1998;391:357-62.
15. Lough J, Barron M, Brogley M, Sugi Y, Bolender DL, Zhu X. Combined BMP-2 and FGF-4, but neither factor alone, induces cardiogenesis in non-precardiac embryonic mesoderm. Dev Biol. 1996;178:198-202.
16. Pfeffer PL, De Robertis EM, Izpisua-Belmonte JC. Crescent, a novel chick gene encoding a Frizzled-like cysteine-rich domain, is expressed in anterior regions during early embryogenesis. Int J Dev Biol. 1997;41:449-58.
17. Dyer LA, Kirby ML. The role of secondary heart fi eld in cardiac development. Dev Biol. 2009;336:137-44.
18. Lin Q, Schwarz J, Bucana C, Olson EN. Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science. 1997;276:1404-7.
19. Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, et al. Isl1 identifi es a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell. 2003;5:877-89.
20. Srivastava D, Thomas T, Lin Q, Kirby ML, Brown D, Olson EN. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet. 1997;16:154-60.
21. Xu H, Morishima M, Wylie JN, Schwartz RJ, Bruneau BG, Lindsay EA, et al. Tbx1 has a dual role in the morphogenesis of the cardiac outfl ow tract. Development. 2004;131: 3217-27.
22. Chapman DL, Garvey N, Hancock S, Alexiou M, Agulnik SI, Gibson-Brown JJ, et al. Expression of the T-box family genes, Tbx1-Tbx5, during early mouse development. Dev Dyn. 1996;206:379-90.
23. von Both I, Silvestri C, Erdemir T, Lickert H, Walls JR, Henkelman RM, et al. Foxh1 is essential for development of the anterior heart fi eld. Dev Cell. 2004;7:331-45.
24. Christoffels VM, Mommersteeg MT, Trowe MO, Prall OW, de Gier-de Vries C, Soufan AT, 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.
25. Christoffels VM, Burch JB, Moorman AF. Architectural plan for the heart: early patterning and delineation of the chambers and the nodes. Trends Cardiovasc Med. 2004;14: 301-7.
26. Naiche LA, Harrelson Z, Kelly RG, Papaioannou VE. T-box genes in vertebrate development. Annu Rev Genet. 2005;39: 219-39.
27. Wilson V, Conlon FL. The T-box family. Genome Biol. 2002; 3:REVIEWS3008.
28. Degnan BM, Vervoort M, Larroux C, Richards GS. Early evolution of metazoan transcription factors. Curr Opin Genet Dev. 2009;19:591-9.
29. Plageman TF Jr, Yutzey KE. T-box genes and heart development: putting the " T " in heart. Dev Dyn. 2005;232:11-20.
30. Agulnik SI, Garvey N, Hancock S, Ruvinsky I, Chapman DL, Agulnik I, et al. Evolution of mouse T-box genes by tandem duplication and cluster dispersion. Genetics. 1996; 144:249-54.
31. Felsenstein J. Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol. 1981;17:368-76.
32. Minguillon C, Gibson-Brown JJ, Logan MP. Tbx4/5 gene duplication and the origin of vertebrate paired appendages. Proc Natl Acad Sci U S A. 2009;106:21726-30.
33. Makarenkov V. T-REX: reconstructing and visualizing phylogenetic trees and reticulation networks. Bioinformatics. 2001;17:664-8.
34. Lardelli M. The evolutionary relationships of zebrafi sh genes tbx6, tbx16/spadetail and mga. Dev Genes Evol. 2003;213: 519-22.
35. Smith J. T-box genes: what they do and how they do it. Trends Genet. 1999;15:154-8.
36. Kitajima S, Takagi A, Inoue T, Saga Y. MesP1 and MesP2 are essential for the development of cardiac mesoderm. Development. 2000;127:3215-26.
37. Boogerd CJ, Moorman AF, Barnett P. Protein interactions at the heart of cardiac chamber formation. Ann Anat. 2009;191:505-17.
38. Zaffran S, Reim I, Qian L, Lo PC, Bodmer R, Frasch M. Cardioblast-intrinsic Tinman activity controls proper diversifi cation and differentiation of myocardial cells in Drosophila. Development. 2006;133:4073-83.
39. Reim I, Frasch M. The Dorsocross T-box genes are key components of the regulatory network controlling early cardiogenesis in Drosophila. Development. 2005;132: 4911-25.
40. Davidson B, Shi W, Levine M. Uncoupling heart cell specifi cation and migration in the simple chordate Ciona intestinalis. Development. 2005;132:4811-8.
41. Carson CT, Kinzler ER, Parr BA. Tbx12, a novel T-box gene, is expressed during early stages of heart and retinal development. Mech Dev. 2000;96:137-40.
42. Horb ME, Thomsen GH. Tbx5 is essential for heart development. Development. 1999;126:1739-51.
43. Zhang C, Basta T, Klymkowsky MW. SOX7 and SOX18 are essential for cardiogenesis in Xenopus. Dev Dyn. 2005;234: 878-91.
44. Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, et al. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell. 2001;104: 619-29.
45. Jerome LA, Papaioannou VE. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet. 2001;27:286-91.
46. Piotrowski T, Ahn DG, Schilling TF, Nair S, Ruvinsky I, Geisler R, et al. The zebrafi sh van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans. Development. 2003;130:5043-52.
47. Frank DU, Fotheringham LK, Brewer JA, Muglia LJ, Tristani-Firouzi M, Capecchi MR, et al. An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome. Development. 2002;129:4591-603.
48. Nowotschin S, Liao J, Gage PJ, Epstein JA, Campione M, Morrow BE. Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart fi eld. Development. 2006;133:1565-73.
49. Maeda J, Yamagishi H, McAnally J, Yamagishi C, Srivastava D. Tbx1 is regulated by forkhead proteins in the secondary heart fi eld. Dev Dyn. 2006;235:701-10.
50. Chen L, Fulcoli FG, Tang S, Baldini A. Tbx1 regulates proliferation and differentiation of multipotent heart progenitors. Circ Res. 2009;105:842-51.
51. Liao J, Aggarwal VS, Nowotschin S, Bondarev A, Lipner S, Morrow BE. Identifi cation of downstream genetic pathways of Tbx1 in the second heart fi eld. Dev Biol. 2008;316: 524-37.
52. Iio A, Koide M, Hidaka K, Morisaki T. Expression pattern of novel chick T-box gene, Tbx20. Dev Genes Evol. 2001;211: 559-62.
53. Chen JN, van Eeden FJ, Warren KS, Chin A, Nusslein- Volhard C, Haffter P, et al. Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafi sh. Development. 1997;124:4373-82.
54. Takeuchi JK, Mileikovskaia M, Koshiba-Takeuchi K, Heidt AB, Mori AD, Arruda EP, et al. Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development. Development. 2005;132:2463-74.
55. Stennard FA, Costa MW, Lai D, Biben C, Furtado MB, Solloway MJ, et al. Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation. Development. 2005;132:2451-62.
56. Dupays L, Kotecha S, Angst B, Mohun TJ. Tbx2 misexpression impairs deployment of second heart fi eld derived progenitor cells to the arterial pole of the embryonic heart. Dev Biol. 2009;333:121-31.
57. Lin L, Cui L, Zhou W, Dufort D, Zhang X, Cai CL, et al. Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis. Proc Natl Acad Sci U S A. 2007;104: 9313-8.
58. Kraus F, Haenig B, Kispert A. Cloning and expression analysis of the mouse T-box gene Tbx18. Mech Dev. 2001;100: 83-6.
59. Mommersteeg MT, Dominguez JN, Wiese C, Norden J, de Gier-de Vries C, Burch JB, et al. The sinus venosus progenitors separate and diversify from the fi rst and second heart fi elds early in development. Cardiovasc Res. 2010;87: 92-101.
60. Cai CL, Martin JC, Sun Y, Cui L, Wang L, Ouyang K, et al. A myocardial lineage derives from Tbx18 epicardial cells. Nature. 2008;454:104-8.
61. Jahr M, Schlueter J, Brand T, Manner J. Development of the proepicardium in Xenopus laevis. Dev Dyn. 2008;237: 3088-96.
62. Wills AA, Holdway JE, Major RJ, Poss KD. Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafi sh. Development. 2008;135:183-92.
63. Christoffels VM, Grieskamp T, Norden J, Mommersteeg MT, Rudat C, Kispert A. Tbx18 and the fate of epicardial progenitors. Nature. 2009;458:E8-9.
64. Molkentin JD, Lin Q, Duncan SA, Olson EN. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. 1997;11:1061-72.
65. Rikin A, Evans T. The tbx/bHLH transcription factor mga regulates gata4 and organogenesis. Dev Dyn. 2010;239: 535-47.
66. S irbu IO, Zhao X, Duester G. Retinoic acid controls heart anteroposterior patterning by down-regulating Isl1 through the Fgf8 pathway. Dev Dyn. 2008;237:1627-35.
67. Ryan K, Chin AJ. T-box genes and cardiac development. Birth Defects Res C Embryo Today. 2003;69:25-37.
68. Amack JD, Wang X, Yost HJ. Two T-box genes play independent and cooperative roles to regulate morphogenesis of ciliated Kupffer's vesicle in zebrafi sh. Dev Biol. 2007;310: 196-210.
69. Kitaguchi T, Mizugishi K, Hatayama M, Aruga J, Mikoshiba K. Xenopus Brachyury regulates mesodermal expression of Zic3, a gene controlling left-right asymmetry. Dev Growth Differ. 2002;44:55-61.
70. King T, Beddington RS, Brown NA. The role of the brachyury gene in heart development and left-right specifi cation in the mouse. Mech Dev. 1998;79:29-37.
71. Hadjantonakis AK, Pisano E, Papaioannou VE. Tbx6 regulates left/right patterning in mouse embryos through effects on nodal cilia and perinodal signaling. PLoS One. 2008;3:e2511.
72. Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R, et al. Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nat Genet. 2001;28: 276-80.
73. Cai CL, Zhou W, Yang L, Bu L, Qyang Y, Zhang X, et al. T-box genes coordinate regional rates of proliferation and regional specifi cation during cardiogenesis. Development. 2005;132:2475-87.
74. Ghosh TK, Song FF, Packham EA, Buxton S, Robinson TE, Ronksley J, et al. Physical interaction between TBX5 and MEF2C is required for early heart development. Mol Cell Biol. 2009;29:2205-18.
75. Garrity DM, Childs S, Fishman MC. The heartstrings mutation in zebrafi sh causes heart/fi n Tbx5 defi ciency syndrome. Development. 2002;129:4635-45.
76. Bruneau BG, Nemer G, Schmitt JP, Charron F, Robitaille L, Caron S, et al. A murine model of Holt-Oram syndrome defi nes roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell. 2001;106:709-21.
77. Kokubo H, Tomita-Miyagawa S, Hamada Y, Saga Y. Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2. Development. 2007;134:747-55.
78. Koibuchi N, Chin MT. CHF1/Hey2 plays a pivotal role in left ventricular maturation through suppression of ectopic atrial gene expression. Circ Res. 2007;100:850-5.
79. M urakami M, Nakagawa M, Olson EN, Nakagawa O. A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome. Proc Natl Acad Sci U S A. 2005;102:18034-9.
80. Lickert H, Takeuchi JK, von Both I, Walls JR, McAuliffe F, Adamson SL, et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature. 2004;432:107-12.
81. Miller SA, Huang AC, Miazgowicz MM, Brassil MM, Weinmann AS. Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression. Genes Dev. 2008;22:2980-93.
82. Takeuchi JK, Lou X, Alexander JM, Sugizaki H, Delgado-Olguin P, Holloway AK, et al. Chromatin remodelling complex dosage modulates transcription factor function in heart development. Nat Commun. 2011;2:187.
83. Fan W, Huang X, Chen C, Gray J, Huang T. TBX3 and its isoform TBX3 2a are functionally distinctive in inhibition of senescence and are overexpressed in a subset of breast cancer cell lines. Cancer Res. 2004;64:5132-9.
84. Yarosh W, Barrientos T, Esmailpour T, Lin L, Carpenter PM, Osann K, et al. TBX3 is overexpressed in breast cancer and represses p14 ARF by interacting with histone deacetylases. Cancer Res. 2008;68:693-9.
85. Georges R, Nemer G, Morin M, Lefebvre C, Nemer M. Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation. Mol Cell Biol. 2008;28:4052-67.
86. Fan C, Chen Q, Wang QK. Functional role of transcriptional factor TBX5 in pre-mRNA splicing and Holt-Oram syndrome via association with SC35. J Biol Chem. 2009;284: 25653-63.
87. Singh R, Horsthuis T, Farin HF, Grieskamp T, Norden J, Petry M, et al. Tbx20 interacts with smads to confi ne tbx2 expression to the atrioventricular canal. Circ Res. 2009; 105:442-52.
88. Ribeiro I, Kawakami Y, Buscher D, Raya A, Rodriguez-Leon J, Morita M, et al. Tbx2 and Tbx3 regulate the dynamics of cell proliferation during heart remodeling. PLoS One. 2007;2:e398.
89. Vance KW, Carreira S, Brosch G, Goding CR. Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas. Cancer Res. 2005;65:2260-8.
90. Harrelson Z, Kelly RG, Goldin SN, Gibson-Brown JJ, Bollag RJ, Silver LM, et al. Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outfl ow tract during heart development. Development. 2004;131:5041-52.
91. Chakraborty S, Combs MD, Yutzey KE. Transcriptional regulation of heart valve progenitor cells. Pediatr Cardiol. 2010;31:414-21.
92. Shirai M, Imanaka-Yoshida K, Schneider MD, Schwartz RJ, Morisaki T. T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and Tgfbeta2 expression and endocardial cushion formation. Proc Natl Acad Sci U S A. 2009;106:18604-9.
93. Koshiba-Takeuchi K, Mori AD, Kaynak BL, Cebra-Thomas J, Sukonnik T, Georges RO, et al. Reptilian heart development and the molecular basis of cardiac chamber evolution. Nature. 2009;461:95-8.
94. Camarata T, Bimber B, Kulisz A, Chew TL, Yeung J, Simon HG. LMP4 regulates Tbx5 protein subcellular localization and activity. J Cell Biol. 2006;174:339-48.
95. Koshiba-Takeuchi K, Takeuchi JK, Arruda EP, Kathiriya IS, Mo R, Hui CC, et al. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nat Genet. 2006;38:175-83.
96. Farin HF, Bussen M, Schmidt MK, Singh MK, Schuster- Gossler K, Kispert A. Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors. J Biol Chem. 2007;282:25748-59.
97. Nadeau M, Georges RO, Laforest B, Yamak A, Lefebvre C, Beauregard J, et al. An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation. Proc Natl Acad Sci U S A. 2010;107:19356-61.
98. Shelton EL, Yutzey KE. Tbx20 regulation of endocardial cushion cell proliferation and extracellular matrix gene expression. Dev Biol. 2007;302:376-88.
99. Shelton EL, Yutzey KE. Twist1 function in endocardial cushion cell proliferation, migration, and differentiation during heart valve development. Dev Biol. 2008;317:282-95.
100. McNally EM, Svensson EC. Setting the pace: Tbx3 and Tbx18 in cardiac conduction system development. Circ Res. 2009;104:285-7.
101. Davenport TG, Jerome-Majewska LA, Papaioannou VE. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Development. 2003;130:2263-73.
102. Hoogaars WM, Tessari A, Moorman AF, de Boer PA, Hagoort J, Soufan AT, et al. The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Cardiovasc Res. 2004;62:489-99.
103. Wiese C, Grieskamp T, Airik R, Mommersteeg MT, Gardiwal A, de Gier-de Vries C, et al. Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circ Res. 2009;104:388-97.
104. Espinoza-Lewis RA, Yu L, He F, Liu H, Tang R, Shi J, et al. Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5. Dev Biol. 2009;327: 376-85.
105. Moskowitz IP, Pizard A, Patel VV, Bruneau BG, Kim JB, Kupershmidt S, et al. The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system. Development. 2004;131: 4107-16.
106. Moskowitz IP, Kim JB, Moore ML, Wolf CM, Peterson MA, Shendure J, et al. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell. 2007;129:1365-76.
107. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39:1890-900.
108. Nemer M. Genetic insights into normal and abnormal heart development. Cardiovasc Pathol. 2008;17:48-54.
109. Mori AD, Bruneau BG. TBX5 mutations and congenital heart disease: Holt-Oram syndrome revealed. Curr Opin Cardiol. 2004;19:211-5.
110. Posch MG, Gramlich M, Sunde M, Schmitt K, Lee SH, Richter S, et al. A gain-of-function TBX20 mutation causes congenital atrial septal defects, patent foramen ovale and cardiac valve defects. J Med Genet. 2010;47;230-5.
111. Kirk EP, Sunde M, Costa MW, Rankin SA, Wolstein O, Castro ML, et al. Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Am J Hum Genet. 2007;81:280-91.
112. Linden H, Williams R, King J, Blair E, Kini U. Ulnar mammary syndrome and TBX3: expanding the phenotype. Am J Med Genet A. 2009;149A:2809-12.
113. Meneghini V, Odent S, Platonova N, Egeo A, Merlo GR. Novel TBX3 mutation data in families with ulnar-mammary syndrome indicate a genotype-phenotype relationship: mutations that do not disrupt the T-domain are associated with less severe limb defects. Eur J Med Genet. 2006;49: 151-8.
114. Meechan DW, Tucker ES, Maynard TM, LaMantia AS. Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/ DiGeorge syndrome. Proc Natl Acad Sci U S A. 2009;106: 16434-45.
115. Lam JT, Moretti A, Laugwitz KL. Multipotent progenitor cells in regenerative cardiovascular medicine. Pediatr Cardiol. 2009;30:690-8.
116. Takeuchi JK, Ohgi M, Koshiba-Takeuchi K, Shiratori H, Sakaki I, Ogura K, et al. Tbx5 specifi es the left/right ventricles and ventricular septum position during cardiogenesis. Development. 2003;130:5953-64.