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During embryonic development of the mammalian cerebral cortex, postmitotic cortical neurons migrate radially from the ventricular zone to the cortical plate.Proper migration involves the correct orientation of migrating neurons and the transition from a multipolar to a mature bipolar morphology.Herein, we report that Myosin-10 (Myo10) plays different roles in the regulation of radial migration in the mouse cortex with its two isoforms.We show that the full-length Myo10 (fMyo10) isoform is located in deeper layers of the cortex and is involved in establishing proper migration orientation, and the headless Myo10 (hMyo10) isoform is required for the transition from multipolar to bipolar morphologies in the intermediate zone.Moreover, we show that fMyo10-dependent orientation of radial migration, but not the hMyo 10-dependent neuronal morphogenesis, is mediated at least in part by the netrin-1 receptor Deleted in Colorectal Cancer (DCC).Our study reveals divergent functions for the two Myo10 isoforms in controlling both the direction of migration and neuronal morphogenesis during radial cortical neuron migration.