Abstract 792: Gata5 and Gata6 are Functionally Redundant for Cardiomyocyte Specification
Defining the transcriptional program that specifies cardiomyocyte fate from uncommitted progenitors is an important goal, since this could impact cellular strategies for treating cardiomyopathies and heart disease. Drosophila genetics identified single transcription factors that are essential for specification of cardiomyocytes from uncommitted mesoderm. A similar specification function has not been shown for orthologous vertebrate genes, even though a number of transcription factors, including those from the GATA, NKX2, MEF2, and TBX gene families, are established as key regulators of normal heart development. This has been presumed to be because paralogous family members compensate for the loss-of-function of individual vertebrate transcription factor genes. The zebrafish model provides advantages to test this hypothesis and define functional redundancies. In zebrafish, defects in gata5 can lead to a loss of myocardial tissue, but most embryos depleted for any single vertebrate gata4/5/6 transcription factor develop a morphogenetic cardiac defect, and cardiomyocytes are specified and differentiate. By targeting the depletion of single or combinations of GATA factors in zebrafish, we show that the GATA gene family is required for cardiomyocyte specification. We find that in zebrafish the gata5 and gata6 genes are redundant for specification of cardiomyocytes. Embryos depleted of these two gene products are heartless. In contrast, embryos depleted of gata4 and gata6, or gata4 and gata5, develop defective heart tubes. Our study identifies a specific pair of vertebrate transcription factor paralogs that is essential for cardiomyocyte specification, and we consider how this relates to mammalian cardiogenesis.