In vivo knockdown of cKit impairs neuronal migration and axonal extension in the cerebral cortex.

The tyrosine kinase receptor cKit and its ligand stem cell factor (SCF) are well known mediators in proliferation, survival, and positive chemotaxis of different cell types in the hematopoietic system. However, and in spite of previous reports showing robust expression of cKit and SCF in the brain during development, their possible function in the cerebral cortex has not been clarified. In this study, embryonic knockdown expression of cKit in the rat cortex by in utero electroporation of specific RNAi resulted in delayed radial migration of cortical neurons. In conditional Nestin-cKit KO homozygous mutants, radial migration in the cortex was also delayed. The opposite phenotype was observed after overexpressing cKit in the cortex: radial migration was accelerated. Callosal fibers electroporated with cKit RNAi were also delayed in their extension within the contralateral cortex and eventually failed to innervate their target area. In vitro experiments showed that, whereas SCF was able to promote migration of cortical neurons, it had no effect on cortical neurite outgrowth. In summary, our results demonstrate that (1) cKit is necessary for radial migration of cortical neurons, probably through SCF binding and (2) cKit is necessary for the correct formation of the callosal projection, most likely by a mechanism not involving SCF.