The Actin-Binding Protein Canoe/AF-6 Forms a Complex with Robo and Is Required for Slit-Robo Signaling during Axon Pathfinding at the CNS Midline

摘要: Axon guidance is a key process during nervous system development and regeneration. One of the best established paradigms to study mechanisms underlying this axon decision whether or not cross midline in Drosophila CNS. An essential regulator that well conserved Slit-Robo signaling pathway. Slit cues act through Robo receptors repel axons from midline. Despite good progress our knowledge about these proteins, intracellular associated with function remain poorly defined. In work, we found scaffolding protein Canoe (Cno), orthologue AF-6/Afadin, for signaling. Cno expressed along longitudinal axonal pioneer tracts, Robo/Fasciclin2-positive aberrantly cno mutant embryos. primary neurons show significant reduction localized growth cone filopodia forms complex vivo. Moreover, commissureless (comm) phenotype (i.e., lack commissures due constitutive surface presentation all neurons) suppressed comm, double-mutant Specific genetic interactions between cno, slit, robo, genes encoding other components pathway, such as Neurexin-IV, Syndecan, Rac GTPases, further confirm functionally interacts Our data argue novel crucial regulating subcellular localization transducing its actin cytoskeleton at