Phases and Mechanisms of Embryonic Cardiomyocyte Proliferation and Ventricular Wall Morphogenesis
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If viewed as a movie, heart morphogenesis appears to unfold in a continuous and seamless manner. At the mechanistic level, however, a series of discreet and separable processes sequentially underlie heart development. This is evident in examining the expansion of the ventricular wall, which accounts for most of the contractile force of each heartbeat. Ventricular wall expansion is driven by cardiomyocyte proliferation coupled with a morphogenetic program that causes wall thickening rather than lengthening. Although most studies of these processes have focused on heart-intrinsic processes, it is increasingly clear that extracardiac events influence or even direct heart morphogenesis. In this review, we specifically consider mechanisms responsible for coordinating cardiomyocyte proliferation and ventricular wall expansion in mammalian development, relying primarily on studies from mouse development where a wealth of molecular and genetic data have been accumulated.
KeywordsCardiomyocyte proliferation Epicardium Placenta–heart IGF2 Congenital heart defects
This review was supported in part by The Magee Prize, Grant #MP001, from the Magee-Womens Research Institute and the Richard King Mellon Foundation, given to YB, MH, and HMS, and by NIH Grant HL070123 provided to HMS.
Compliance with Ethical Standards
Conflict of interest
All authors declare that they have no conflicts of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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