Maternal induction of ventral fate by zebrafish radar.

Abstract

In vertebrate embryos, maternal determinants are thought to preestablish the dorsoventral axis by locally activating zygotic ventral- and dorsal-specifying genes, e.g., genes encoding bone morphogenetic proteins (BMPs) and BMP inhibitors, respectively. Whereas the canonical Wntbeta-catenin pathway fulfills this role dorsally, the existence of a reciprocal maternal ventralizing signal remains hypothetical. Maternal noncanonical WntCa(2+) signaling may promote ventral fates by suppressing Wntbeta-catenin dorsalizing signals; however, whether any maternal determinant is directly required for the activation of zygotic ventral-specifying genes is unknown. Here, we show that such a function is achieved, in part, in the zebrafish embryo by the maternally encoded transforming growth factor beta (TGF-beta) signaling molecule, Radar. Loss-of-function experiments, together with epistasis analyses, identify maternal Radar as an upstream activator of bmps expression. Maternal induction of bmps by Radar is essential for zebrafish development as its removal results in larval-lethal dorsalized phenotypes. Double-morphant analyses further suggest that Radar functions through the TGF-beta receptor Alk8 to initiate the expression of bmp genes. Our results support the existence of a previously uncharacterized maternal ventralizing pathway. They might further indicate that maternal TGF-betaRdr and WntCa(2+) pathways complementarily specify ventral cell fates, with the former triggering bmps expression and the latter indirectly repressing genes encoding BMP antagonists.