Heart Development: Gene Control

Paul A Krieg, University of Arizona College of Medicine, Tucson, Arizona, USA

Published online: June 2010

DOI: 10.1002/9780470015902.a0000736.pub2

All creatures from flies to humans possess a heart-like contractile organ responsible for movement of fluid through the body. Molecular studies have revealed a remarkable degree of evolutionary conservation in the genetic pathways underlying heart development. In Drosophila, the transcription regulatory proteins TINMAN, PANNIER, MEF2, plus members of the TBX and HAND families are required for regulation of heart muscle differentiation and correct morphogenesis of the heart. Expression of the cardiac transcription factors is regulated by growth factor signalling from adjacent tissues. In vertebrates, members of precisely the same transcription factor families are required for heart development and their expression is also subject to growth factor regulation. One major difference is that higher organisms usually express several members of each protein family, leading to at least partial functional redundancy. In both flies and mammals, several distinct transcription regulatory proteins interact both genetically and physically to precisely regulate transcription of the structural, morphological and physiological genes required for establishment of correct heart structure and function.

Key Concepts:

  • The transcription regulatory system required for development of the heart involves members of several distinct transcription factor families.
  • Interactions between a number of distinct transcription factors are essential for gene regulatory function.
  • Genetic regulation of heart development is evolutionarily conserved.

Keywords: Tinman; Nkx2-5; GATA factors; MEF2; Tbx; Hand; Isl1

Figure 1. Overview of the genetic pathways regulating embryonic heart development. The boxes are somewhat arbitrary but broadly represent the temporal sequence of the cardiogenic programme. Red double-headed arrows indicate characterised protein–protein interactions. Blue arrows indicate transcriptional regulation between categories of genes. Information on gene names is contained in the text.
close
 References
    Cai CL, Liang X, Shi Y et al. (2003) Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Developmental Cell 5: 877–889.
    Dodou E, Verzi MP, Anderson JP, Xu SM and Black BL (2004) Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. Development 131: 3931–3942.
    Durocher D, Charron F, Warren R, Schwartz RJ and Nemer M (1997) The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors. EMBO Journal 16: 5687–5696.
    Foley A and Mercola M (2004) Heart induction: embryology to cardiomyocyte regeneration. Trends in Cardiovascular Medicine 14: 121–125.
    Frasch M (1995) Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo. Nature 374: 464–467.
    Ghosh TK, Song FF, Packham EA et al. (2009) Physical interaction between TBX5 and MEF2C is required for early heart development. Molecular and Cellular Biology 29: 2205–2218.
    Han Z, Yi P, Li X and Olson EN (2006) Hand, an evolutionarily conserved bHLH transcription factor required for Drosophila cardiogenesis and hematopoiesis. Development 133: 1175–1182.
    Harvey RP (2002) Patterning the vertebrate heart. Nature Reviews Genetics 3: 544–556.
    Hiroi Y, Kudoh S, Monzen K et al. (2001) Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nature Genetics 28: 276–280.
    Hoover LL, Burton EG, Brooks BA and Kubalak SW (2008) The expanding role for retinoid signaling in heart development. Scientific World Journal 8: 194–211.
    Karamboulas C, Dakubo GD, Liu J et al. (2006) Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis. Journal of Cell Science 119: 4315–4321.
    Klaus A, Saga Y, Taketo MM, Tzahor E and Birchmeier W (2007) Distinct roles of Wnt/beta-catenin and Bmp signaling during early cardiogenesis. Proceedings of the National Academy of Sciences of the USA 104: 18531–18536.
    Klinedinst SL and Bodmer R (2003) Gata factor Pannier is required to establish competence for heart progenitor formation. Development 130: 3027–3038.
    Kuo CT, Morrisey EE, Anandappa R et al. (1997) GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes and Development 11: 1048–1060.
    Li P, Pashmforoush M and Sucov HM (2010) Retinoic acid regulates differentiation of the secondary heart field and TGFbeta-mediated outflow tract septation. Developmental Cell 18: 480–485.
    Lyons I, Parsons LM, Hartley L et al. (1995) Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeobox gene Nkx-2.5. Genes and Development 9: 1654–1666.
    McFadden DG, Barbosa AC, Richardson JA et al. (2005) The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner. Development 132: 189–201.
    Molkentin JD, Lin Q, Duncan SA and Olson EN (1997) Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes and Development 11: 1061–1072.
    Morin S, Pozzulo G, Robitaille L, Cross J and Nemer M (2005) MEF2-dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters. Journal of Biological Chemistry 280: 32272–32278.
    Overbeek PA (1997) Right and left go dHand and eHand. Nature Genetics 16: 119–121.
    Pandur P, Läsche M, Eisenberg LM and Kühl M (2002) Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 418: 636–641.
    Plageman TF Jr and Yutzey KE (2005) T-box genes and heart development: putting the “T” in heart. Developmental Dynamics 232: 11–20.
    Reim I and Frasch M (2005) The dorsocross T-box genes are key components of the regulatory network controlling early cardiogenesis in Drosophila. Development 132: 4911–4925.
    Sepulveda JL, Belaguli N, Nigam V et al. (1998) GATA-4 and Nkx-2.5 coactivate Nkx-2 DNA binding targets: role for regulating early cardiac gene expression. Molecular and Cellular Biology 18: 3405–3415.
    Sorrentino RP, Gajewski KM and Schulz RA (2005) GATA factors in Drosophila heart and blood cell development. Seminars in Cell and Developmental Biology 16: 107–116.
    Stennard FA, Costa MW, Elliott DA et al. (2003) Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Developmental Biology 262: 206–224.
    Tanaka M, Schinke M, Liao HS, Yamasaki N and Izumo S (2001) Nkx2-5 and Nkx2-6, homologs of Drosophila tinman, are required for development of the pharynx. Molecular and Cellular Biology 21: 4391–4398.
    Tu CT, Yang TC and Tsai HJ (2009) Nkx2-7 and Nkx2-5 function redundantly and are required for cardiac morphogenesis of zebrafish embryos. PloS One 4: e4249.
    Zhao R, Watt AJ, Battle MA et al. (2008) Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice. Developmental Biology 317: 614–619.
 Further Reading
    book Rosenthal N and Harvey RP (2010) Heart Development and Regeneration. San Diego: Academic Press.

Related Sub-Topics:

Genes, Molecules and Cellular Processes | Organogenesis
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Heart Development: Gene Control
 
How to Cite close
Krieg, Paul A(Jun 2010) Heart Development: Gene Control. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000736.pub2]