Function of GATA -4/5/6 genes in embryonic cardiogenesis

Abstract

The GATA factors have been implicated in heart development. It is not clear at which steps of cardiogenesis GATA factors play critical roles. Each Xenopus GATA-4/5/6 gene is expressed in heart and endoderm derived tissues. During embryogenesis, transcripts of each gene localize throughout the developing cardiogenic region. Transcription of these genes is intimately associated with the specification of cardiac progenitors. Ectopic expression of each gene is specifically capable of activating during embryogenesis the transcription of the cardiac genes encoding cardiac actin and myosin heavy chain. These data indicate a role of GATA factors in the regulation of cardiac-specific differentiation programs.;The expression patterns of cGATA-4/5/6 overlap but extend beyond the presumptive cardiornyocyte population expressing cNkx-2.5. To investigate the functional specificity, antisense oligomers were used to deplete the transcripts of cGATA-4/5/6 genes during early development. Only when oligomers are used to target transcripts for all three genes, a high percentage of the embryos develop abnormal hearts related to the failure to form a normal primitive heart tube. Therefore, each of the cGATA-4/5/6 genes functions in a common pathway, at the time of cardiac crescent forms, for regulating early embryonic cardiac morphogenesis, apparently associated with embryonic folding or the migration of primordia to form a primitive tube.;In vitamin A deficient quail embryos, which develop abnormal hearts with an enlarged ventricle and an absence of the inflow tract, GATA-4 gene expression is down-regulated, especially at the posterior region where the inflow tract should form. The GATA-4 expression and the vitamin A deficient phenotype can be rescued by retinoid acid at the same developmental time. In retinoid acid treated Xenopus embryos, which are blocked for the differentiation of myocardium, expression of GATA-4 gene is expanded. These data indicate that GATA-4 might be a mediator in retinoid acid signaling pathway for heart tube formation.;Finally, the preliminary results demonstrate that GATA-4/5/6 genes might negatively regulate the expression of Nkx2 genes during cardiogenesis. Therefore, it is clear that GATA factors can function at multiple steps to regulate differentiation, morphogenesis, and patterning of the embryonic heart.