17 - GATA Transcription Factors and Cardiac Development

Abstract

This chapter summarizes the current understanding of the role of three GATA family transcription factors, GATA-4,-5, and -6, in cardiovascular development. It is found that GATA family members expressed in temporally distinct patterns in the developing mammalian heart. In addition, GATA-6 is expressed in both arterial and venous SMCs, suggesting a potential role for this protein in the development of the vasculature. GATA-4,-5, and -6 can each bind to the transcriptional regulatory regions of multiple cardiac promoters and enhancers, and transactivate these transcriptional regulatory elements in nonmuscle cells. Each of these factors share two unique and independent transcriptional activation domains. Gene targeting experiments have demonstrated a necessary role for GATA-4 in regulating the second stage of cardiac development in the migration of specified procardiomyocytes from the dorsolateral region of the embryo to form the ventral linear heart tube. Chimera experiments suggest that GATA-4 is required to initiate and/or maintain the ventral morphogenic signal rather than to act as a regulator of cardiomyocyte responsiveness to this signal. GATA-6 is also required for early embryonic viability and its precise role in cardiovascular development is currently under investigation. In contrast, GATA-5 does not appear to be required for the development of the heart and vasculature. Finally, preliminary evidence suggests that GATA-4 and GATA-6 may belong to a common developmental pathway in which GATA-4 normally down regulates the expression of GATA-6 in the heart and extra embryonic membranes.