Transmembrane signaling in the regulation of neural crest and eye development

Wnts are secreted signaling molecules involved in a large number of developmental processes. For example, Wnt/frizzled signaling is proposed to regulate the early steps of neural crest formation. Wnts also induce posterior neural character from anterior neural tissues in parallel with neural crest induction. Some have therefore proposed that neural crest induction by Wnts is a secondary consequence of posteriorization. However, whether Wnts induce neural crest directly or indirectly has not been studied. In this work, we present evidence that neural crest induction by canonical Wnt signaling is distinct and independent of Wnt-mediated posteriorization of neural tissues. Previous work in this laboratory showed that frizzled 3 is required for neural crest induction and that a frizzled 3 interacting protein, Kermit/GIPC is required for frizzled induced neural crest formation in ectodermal explants. However, depletion of Kermit/GIPC does not disrupt neural crest induction in whole embryos. A second Kermit/GIPC homologue, Kermit-2 was identified to test for redundant function of Kermit and Kermit-2. To our surprise, Kermit-2 does not interact with frizzled receptors and is not redundant with the first Kermit. We found that Kermit-2 interacts with the IGF1 receptor and is required for IGF induced eye development in embryos. Our work demonstrates the direct effect of Wnt/frizzled signaling on neural crest induction and provides one of the first functional studies of GIPC