Bmp2 and Gata4 function additively to rescue heart tube development in the absence of retinoids.

We used the vitamin A-deficient (VAD) quail model to investigate the retinoid-dependent mechanism that regulates heart tube development. We showed previously that decreased levels of Gata4 in cardiogenic mesoderm and endoderm correlate with the cardiomyopathy caused by VAD, but that this could be rescued by transplanting normal anterior endoderm. Bmp2 is a known cardiogenic factor that is expressed normally in lateral plate mesoderm and cardiac-associated pharyngeal endoderm. Here we show that (like Gata4) transcripts encoding Bmp2 and BMP-dependent signaling activity are decreased throughout the heart-forming region of the VAD embryo. Addition of Bmp2 protein or forced expression of Gata4 in cultured VAD embryos leads to a partial rescue of the cardiomyopathy, and addition of both Bmp2 and Gata4 has an additive positive effect. Our data are consistent with a requirement for retinoid signaling to maintain expression of Bmp2, which regulates Gata4, and in addition acts with Gata4 to regulate genes important for normal morphogenesis of the primitive heart tube.