Embryonic Stem Cells: A Biological Tool to Translate the Mechanisms of Heart Development

Heart organogenesis is sensitive to both genetic and environmental factors and heart malformations account for the majority of birth defects. The development of the mammalian heart is a complex morphogenetic process that ultimately results in a contractile, four-chambered organ that is formed from progenitor cells of mesodermal and neural crest origins. Studies in animal models with primitive hearts such as drosophila, zebrafish, and xenopus have provided important insights into the way the heart begins to form and the molecular cues that guide the early stages of cardiac morphogenesis. Much of what we know about the development of the heart in higher vertebrates comes mostly from embryological investigations in chick and mouse. In addition, genetic studies in zebrafish and mouse, including loss- and gain-of-function approaches, have been especially valuable for gaining information about the role of individual genes in heart development. However, the various animal models also have a number of limitations regarding lack of genetic tools (chick, xenopus), inaccessibility to observation and embryological manipulation (mouse), or unsuitability for high-throughput screens to identify pharmacologic compounds to treat cardiac defects. Mouse embryonic stem (ES) cells give rise to a wide variety of organ-specific cell types, offering an accessible and relevant system to investigate how cell lineages emerge and grow. The ES cell model is particularly pertinent for studying the molecular mechanisms regulating the specification and differentiation of cardiovascular progenitor cells, because these cells appear relatively early during embryonic development and ES cell differentiation. This chapter reviews a selective number of studies that have applied the in vitro differentiation of embryonic stem cells toward understanding the regulatory steps of cardiac development.