Members of the Wnt family of extracellular glycoproteins function during development and in adult tissues to control different cellular processes including cell fate specification and cell polarity. The ability of Wnts to regulate distinct cellular activities is dependent on the activation of different Wnt signaling pathways. In Drosophila, Wnt signaling has been shown to either influence cell fate decisions (segment polarity pathway, Wnt/Wg-pathway) or tissue polariy (also known as planar cell polarity pathway). In current models of the Wnt/Wg- pathway, members of the Frizzled family transduce the Wnt signal across the membrane thereby activating the phosphoprotein dishevelled. Activated dishevelled (dsh) functions through a protein complex comprising GSK-3ß, APC, and Axin/Conductin to stabilize b-catenin. The latter than is able to function as a transcriptional activator in conjunction with transcription factors of the TCF/Lef family. Beside its role in determining cell fate, dsh plays a role in the planar cell polarity pathway. In Drosophila this pathway includes the small GTPases Rho and Rac, Jun-N-terminal kinase, the cytoplasmic protein Multiple Wing Hair and the novel transmembrane proteins Fuzzy, Inturned and Strabismus.

In vertebrates, Wnts are divided into two functional classes. Whereas the Wnt-1/Wg signaling cascade (in analogy to the segment polarity pathway in Drosophila) is well understood, relatively less is known how signals of the Wnt-5A class are translated inside the cell. Although possible, there is no evidence up to now that the Wnt-5A pathway might be identical to the planar polarity pathway in Drosophila. Xwnt-5A is able to activate phospholipase C in a G-protein coupled manner leading to the increase of intracellular Ca2+-transients.

Based on these observations we follow the following questions and topics:

1. Identification of new signal transducers of classical and non-classical Wnt signaling pathways.

2. What is the role of different Wnts in mesodermal and neural patterning in Xenopus and Zebrafish?

3. How is the TCF/Lef-b-catenin complex regulated?

4. What is the role of Xwnt-8 and Xwnt-5A in regulating gastrulation movements?