Centrosome motility is essential for initial axon formation in the neocortex

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 cort...

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Bibliographic Details
Published in:The Journal of neuroscience 2010-08, Vol.30 (31), p.10391-10406
Main Authors: de Anda, Froylan Calderon, Meletis, Konstantinos, Ge, Xuecai, Rei, Damien, Tsai, Li-Huei
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Autoantigens - metabolism
Axons - metabolism
Cell Cycle Proteins - metabolism
Cell Death
Cell Line
Cell Movement - physiology
Cell Polarity
Cells, Cultured
Centrosome - metabolism
Down-Regulation
Electroporation
Embryo Culture Techniques
Fluorescent Antibody Technique
Golgi Apparatus - metabolism
Humans
Mice
Microscopy, Confocal
Microtubules - metabolism
Neocortex - metabolism
Neurons - metabolism
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0381-10.2010