Distinct Frizzled receptors independently mediate endomesoderm specification and primary archenteron invagination during gastrulation in Nematostella

Endomesodermal cell fate specification and archenteron formation during gastrulation are tightly linked developmental processes in most metazoans. However, studies have shown that in the anthozoan cnidarian Nematostella vectensis, Wnt/β-catenin (cWnt) signaling-mediated endomesodermal cell fate specification can be experimentally uncoupled from Wnt/Planar Cell Polarity (PCP) signaling-mediated primary archenteron invagination. The upstream signaling mechanisms regulating cWnt signaling-dependent endomesoderm cell fate specification and Wnt/PCP signaling-mediated primary archenteron invagination in Nematostella embryos are not well understood. By screening for potential upstream mediators of cWnt and Wnt/PCP signaling, we identified two Nematostella Frizzled homologs that are expressed early in development. NvFzd1 is expressed maternally and in a broad pattern during early development while NvFzd10 is zygotically expressed at the animal pole in blastula stage embryos and is restricted to the invaginating cells of the presumptive endomesoderm. Molecular and morphological characterization of NvFzd1 and NvFzd10 knock-down phenotypes provide evidence for distinct regulatory roles for the two receptors in endomesoderm cell fate specification and primary archenteron invagination. These results provide further experimental evidence for the independent regulation of endomesodermal cell fate specification and primary archenteron invagination during gastrulation in Nematostella. Moreover, these results provide additional support for the previously proposed two-step model for the independent evolution of cWnt-mediated cell fate specification and Wnt/PCP-mediated primary archenteron invagination.