Ror2-cytoskeleton interactions in morphogenesis

• Applicant: Professorin Dr. Alexandra Schambony
• Subject Area: Developmental Biology ; Cell Biology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236616708

Morphogenetic movements are coordinated mass cell movements, which shape an embryo during its development and are controlled by different signaling pathways including non-canonical Wnt-pathways such as the planar cell polarity or PCP pathway. The receptor tyrosine kinase Ror2 plays an important role in the regulation of PCP signaling and morphogenesis in vertebrates. Ror2 loss-of-function results in morphogenetic defects such as shortened body axis and short limbs and tails (van Bokhoven et al., 2000; Oishi et al., 2003; Schambony and Wedlich, 2007). In addition to its role in Wnt signaling pathways, Ror2 has been shown influence cell morphology by binding to Filamin A (Nishita et al., 2006; Nomachi et al., 2008). However, little is known about the interaction of Ror2 with the cytoskeleton and its contribution to Ror2 function in morphogenesis. Coordinating cell polarity and regulation of cytoskeleton remodelling and cell migration are crucial in morphogenetic movements. Our preliminary data revealed an unexpectedly high percentage of cytoskeleton-associated proteins as Ror2 binding partners. These results suggest a significant contribution of cytoskeleton interactions to Ror2 function. Thus, Ror2 could play a central role in the coordination of signal reception and cytoskeleton remodeling in morphogenesis. Here, we propose to study the biochemical, biophysical and functional interaction between Ror2 and the cytoskeleton in more detail using cell, tissue and in vivo model systems.

• DFG Programme: Research Grants