Wnt genes encode highly conserved glycoproteins that play a variety of roles at different stages of development. Their functions include the regulation of cell proliferation, cell fate... Show moreWnt genes encode highly conserved glycoproteins that play a variety of roles at different stages of development. Their functions include the regulation of cell proliferation, cell fate specification, cell polarity, apoptosis, stem cell self-renewal, cell migration and tissue homeostasis. In the nervous system, Wnts act in neuronal migration, axon path finding, dendritic morphogenesis and synapse differentiation. Wnts serve as both attractive and repulsive cues during axon guidance, mediated through distinct mechanisms. The attractive responses to axonal growth are guided, at least in part, by the Frizzled receptors. Repulsive cues, on the other hand, can be mediated by the tyrosine kinase receptor Ryk. The aim of this thesis is the dissection of the basic biological and likely evolutionary conserved, functions of Wnt signaling through two different receptor families, the Ryks and Rors. We have employed genetic, biochemical, and electrophysiological approaches in order to understand the functions of these receptors and the pathways that they mediate. The studies in this thesis present novel insights into the biochemical mechanisms and the biological relevance of Wnt/Ror and Wnt/Ryk signaling for the development of a complex nervous system. Our findings can provide a starting point for the design of future therapeutic approaches for modulating the Wnt-Ryk and or Wnt-Ror pathways to treat post-injury nervous system lesions and aid neuronal regeneration. Show less
