Maternal induction of ventral fate by zebrafish radar

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 Wnt/β-catenin pathway fulfills this role dorsally, the existence of a reciprocal maternal signal remains hypothetical. Maternal noncanonical Wnt/Ca²⁺ signaling may promote ventral fates by suppressing Wnt/β-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 β (TGF-β) 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-β 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-β/Rdr and Wnt/Ca²⁺ pathways complementarily specify ventral cell fates, with the former triggering bmps expression and the latter indirectly repressing genes encoding BMP antagonists.