Neural precursors are generated in proliferative zones, before migrating to directed locations where they undergo maturation and become functional neurons. Studies in Drosophila first suggested Numb played a role in cell migration when mutants displayed defective glial migration along axonal tracts. Since then, a mechanism has been discovered through which Numb binds chemotactic signaling receptors, forming a scaffold for atypical PKC (aPKC) recruitment to the receptor complex. Once activated, aPKC phosphorylates Numb, thus promoting a positive feed-forward response that potentiates Numb-chemotactic receptor binding and subsequent endosomal complex formation. Endocytosis supports the relocalization of the chemotactic receptor to the front of the cell to promote receptor-mediated directional migration in response to receptor activation.
