title: In vivo knockdown of cKit impairs neuronal migration and axonal extension in the cerebral cortex.
abstract: 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.
authors.affiliation: State Key Laboratory of Neuroscience, Institute of Neuroscience (ION), Shanghai Institutes for Biological Sciences (SIBS), Shanghai, 200031, China; CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences (SIBS), Shanghai, 200031, China.
authors.forename: Patricia
authors.initials: P
authors.lastname: Guijarro
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanting
authors.initials: Y
authors.lastname: Ying
authors.forename: Yini
authors.initials: Y
authors.lastname: Yao
authors.forename: Xiong
authors.initials: X
authors.lastname: Jieyi
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Yuan
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D055785:Gene Knockdown Techniques / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit
keywords: SCF; cKit; callosal projection; cortex; radial neuronal migration