Project Summary

Wnt signaling plays a dominant role during the development of the neural crest, a highly migratory cell population that has the ability to differentiate into a vast array of cell types. Canonical Wnt signaling is required for neural crest induction. Non-canonical, i.e. ß-catenin independent Wnt signals have been shown to be necessary for neural crest migration, while neural crest differentiation is affected by canonical Wnt signaling. Thus, it seems likely that post-induction neural crest development is modulated by a network of canonical and non-canonical Wnt signals reminiscent of the regulation of other morphogenetic processes. However, little is known about the contributions and the cross-talk of canonical and non-canonical pathways in the different phases of post-induction neural crest development.

Previously, we have shown that PTK7 is required for Xenopus neural crest migration and interacts with Ror2. The role of Ror2 in neural crest development has so far not been studied, but our preliminary data suggest that Ror2 influences multiple phases of neural crest development. This assumption is also sup-ported by the finding that Ror2 knock-out mice and patients bearing the Ror2 loss-of-function mutation causative of Robinow syndrome show cranio-facial deformations.  Based on our previous work, we hypothesize that neural crest development is regulated by a network of different Wnt-pathways. PTK7 and Ror2 are likely modulating the interplay of these different signaling cascades, because we and others have shown that they regulate canonical and non-canonical Wnt path-ways. Both proteins can antagonize the canonical Wnt-pathway. In addition, PTK7 acts as a regulator of PCP, while Ror2 acts in different non-canonical pathways including the PCP pathway and the Wnt-5a/Ror2 pathway described by us. Thus, PTK7 and Ror2 could provide a molecular mechanism to mediate the cross-talk between canonical and non-canonical pathways in neural crest development. Here, we will address how canonical and non-canonical Wnt signaling affect neural crest development and which role PTK7 and Ror2 play in this process.