Analyzing canoncical versus non-canoncical Wnt signalling in neural crest migration and differentiation

• Antragstellerinnen: Professorin Dr. Annette Borchers; Professorin Dr. Alexandra Schambony
• Fachliche Zuordnung: Hämatologie, Onkologie
• Förderung: Förderung von 2007 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 45707573

Wnt signaling plays a dominant role during the development of the neural crest (NC), a highly migratory cell population that has the ability to differentiate into a vast array of cell types. Canonical Wnt signaling is required for NC induction, while non-canonical, β-catenin independent, Wnt signals, are necessary for NC migration. As canonical Wnt signaling also affects NC specification, it seems likely that post-induction NC 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 NC development. 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 pathways. PTK7 is a regulator of PCP signaling (Lu et al., 2004), while Ror2 acts in multiple non-canonical pathways including the PCP pathway (Yamamoto et al., 2008) and the Wnt- 5a/Ror2 pathway described by us (Schambony and Wedlich, 2007). Interestingly, both proteins can antagonize the canonical Wnt-pathway ((Witte et al., 2010) and unpublished data). Furthermore, we demonstrated that PTK7 is required for NC migration and our preliminary data suggest that Ror2 also plays a role in NC development. Thus, PTK7 and Ror2 could provide the molecular toolkit to mediate the cross-talk between canonical and non-canonical pathways during NC development.

• DFG-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 942: WNT signalling in development and tumor progression