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Centrosome Motility is Essential for Initial Axon Formation in the Neocortex

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Journal J Neurosci
Specialty Neurology
Date 2010 Aug 6
PMID 20685982
Citations 70
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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.

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References
1.
Xie Z, Moy L, Sanada K, Zhou Y, Buchman J, Tsai L . Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool. Neuron. 2007; 56(1):79-93. PMC: 2642594. DOI: 10.1016/j.neuron.2007.08.026. View

2.
Gupta S, Meiri K, Mahfooz K, Bharti U, Mani S . Coordination between extrinsic extracellular matrix cues and intrinsic responses to orient the centrosome in polarizing cerebellar granule neurons. J Neurosci. 2010; 30(7):2755-66. PMC: 2846173. DOI: 10.1523/JNEUROSCI.4218-09.2010. View

3.
Prasad B, Clark S . Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans. Development. 2006; 133(9):1757-66. DOI: 10.1242/dev.02357. View

4.
Rivas R, Hatten M . Motility and cytoskeletal organization of migrating cerebellar granule neurons. J Neurosci. 1995; 15(2):981-9. PMC: 6577828. View

5.
Conde C, Caceres A . Microtubule assembly, organization and dynamics in axons and dendrites. Nat Rev Neurosci. 2009; 10(5):319-32. DOI: 10.1038/nrn2631. View