In nervous systems with bilateral symmetry, many neurons project axons across the midline to the opposite side. In each segment of the Drosophila embryonic nervous system, axons that display this projection pattern choose one of two distinct tracts: the anterior or posterior commissure. Commissure choice is controlled by Derailed, an atypical receptor tyrosine kinase expressed on axons projecting in the anterior commissure. Here we show that Derailed keeps these axons out of the posterior commissure by acting as a receptor for Wnt5, a member of the Wnt family of secreted signalling molecules. Our results reveal an unexpected role in axon guidance for a Wnt family member, and show that the Derailed receptor is an essential component of Wnt signalling in these guidance events.
Multiple sclerosis (MS), the most common neurological disorder diagnosed in young adults, is characterized by autoimmune demyelination in the central nervous system (CNS). Promotion of remyelination in the brain and spinal cord is a potential strategy for therapeutic intervention in MS and other demyelinating diseases. Recent studies have shown that the development of oligodendrocytes, the myelin-forming cells of the CNS, is extensively controlled by growth factors. These factors regulate the proliferation, migration, differentiation, survival and regeneration of oligodendroglial cells and the synthesis of myelin, and often interact in a complex manner. Moreover, insulin-like growth factor I (IGF-I) has proven effective for therapy of experimental autoimmune encephalomyelitis (EAE), an animal model of autoimmune demyelination. In this review we summarize recent findings on the regulation of oligodendrocyte development and CNS myelination by growth factors, and discuss these findings in the context of possible clinical application for the therapy of neurological disease in humans.
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