Retinoid signaling required for normal heart development regulates GATA-4 in a pathway distinct from cardiomyocyte differentiation

Vitamin A is essential for normal embryonic cardiogenesis. The vitamin A-de ficient phenotype ill the avian embryo includes an abnormal heart tube clos ed at the sinus venosus and the absence of large vessels that normally conn ect the embryonic heart to the developing circulatory system. III vitamin A -deficient embryos the expression of cardiomyocyte differentiation genes, i ncluding atrial-specific myosin heavy chain, ventricular-specific myosin, a nd sarcomeric myosins as well as the putative cardiomyocyte specification g ene Nkx-2.5, is not altered. However, the expression of transcription facto r GATA-4 is severely decreased in the heart-forming regions of vitamin A-de ficient stage 7-10 embryos. Significantly, GATA-4 transcripts are completel y lacking in the lateral mesoderm posterior to the heart, in the area of th e developing cardiac inflow tract that later displays prominent morphologic al defects, including a closed nonseptated heart lacking a sinus venosus. T he administration of retinol to the vitamin A-deficient embryo restores GAT A-4 expression and completely rescues the vitamin A-deficient phenotype. Ou r results indicate that GATA-4 is a component of the retinoid-mediated card iogenic pathway unlinked to cardiomyocyte differentiation, but involved in the morphogenesis of the posterior heart tube and the development of the ca rdiac inflow tract. (C) 1999 Academic Press.