title: Centrosome motility is essential for initial axon formation in the neocortex.
abstract: The mechanisms underlying the normal development of neuronal morphology remain a fundamental question in neurobiology. Studies in cultured neurons have suggested that the position of the centrosome and the Golgi may predict the site of axon outgrowth. During neuronal migration in the developing cortex, however, the centrosome and Golgi are oriented toward the cortical plate at a time when axons grow toward the ventricular zone. In the current work, we use in situ live imaging to demonstrate that the centrosome and the accompanying polarized cytoplasm exhibit apical translocation in newborn cortical neurons preceding initial axon outgrowth. Disruption of centrosomal activity or downregulation of the centriolar satellite protein PCM-1 affects axon formation. We further show that downregulation of the centrosomal protein Cep120 impairs microtubule organization, resulting in increased centrosome motility. Decreased centrosome motility resulting from microtubule stabilization causes an aberrant centrosomal localization, leading to misplaced axonal outgrowth. Our results reveal the dynamic nature of the centrosome in developing cortical neurons, and implicate centrosome translocation and microtubule organization during the multipolar stage as important determinants of axon formation.
authors.affiliation: Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. fcaldero@mit.edu
authors.forename: Froylan Calderon
authors.initials: FC
authors.lastname: de Anda
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Meletis
authors.forename: Xuecai
authors.initials: X
authors.lastname: Ge
authors.forename: Damien
authors.initials: D
authors.lastname: Rei
authors.forename: Li-Huei
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D015536:Down-Regulation; D018274:Electroporation; D046149:Embryo Culture Techniques; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism; D019579:Neocortex / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D018797:Cell Cycle Proteins; C525527:Cep120 protein, mouse; C086074:PCM1 protein, human