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Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex

During cerebral cortex development, pyramidal neurons migrate through the intermediate zone and integrate into the cortical plate. These neurons undergo the multipolar–bipolar transition to initiate radial migration. While perturbation of this polarity acquisition leads to cortical malformations, ho...

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Autores principales: Ye, Tao, Ip, Jacque P. K., Fu, Amy K. Y., Ip, Nancy Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164783/
https://www.ncbi.nlm.nih.gov/pubmed/25189171
http://dx.doi.org/10.1038/ncomms5826
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author Ye, Tao
Ip, Jacque P. K.
Fu, Amy K. Y.
Ip, Nancy Y.
author_facet Ye, Tao
Ip, Jacque P. K.
Fu, Amy K. Y.
Ip, Nancy Y.
author_sort Ye, Tao
collection PubMed
description During cerebral cortex development, pyramidal neurons migrate through the intermediate zone and integrate into the cortical plate. These neurons undergo the multipolar–bipolar transition to initiate radial migration. While perturbation of this polarity acquisition leads to cortical malformations, how this process is initiated and regulated is largely unknown. Here we report that the specific upregulation of the Rap1 guanine nucleotide exchange factor, RapGEF2, in migrating neurons corresponds to the timing of this polarity transition. In utero electroporation and live-imaging studies reveal that RapGEF2 acts on the multipolar–bipolar transition during neuronal migration via a Rap1/N-cadherin pathway. Importantly, activation of RapGEF2 is controlled via phosphorylation by a serine/threonine kinase Cdk5, whose activity is largely restricted to the radial migration zone. Thus, the specific expression and Cdk5-dependent phosphorylation of RapGEF2 during multipolar–bipolar transition within the intermediate zone are essential for proper neuronal migration and wiring of the cerebral cortex.
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spelling pubmed-41647832014-09-22 Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex Ye, Tao Ip, Jacque P. K. Fu, Amy K. Y. Ip, Nancy Y. Nat Commun Article During cerebral cortex development, pyramidal neurons migrate through the intermediate zone and integrate into the cortical plate. These neurons undergo the multipolar–bipolar transition to initiate radial migration. While perturbation of this polarity acquisition leads to cortical malformations, how this process is initiated and regulated is largely unknown. Here we report that the specific upregulation of the Rap1 guanine nucleotide exchange factor, RapGEF2, in migrating neurons corresponds to the timing of this polarity transition. In utero electroporation and live-imaging studies reveal that RapGEF2 acts on the multipolar–bipolar transition during neuronal migration via a Rap1/N-cadherin pathway. Importantly, activation of RapGEF2 is controlled via phosphorylation by a serine/threonine kinase Cdk5, whose activity is largely restricted to the radial migration zone. Thus, the specific expression and Cdk5-dependent phosphorylation of RapGEF2 during multipolar–bipolar transition within the intermediate zone are essential for proper neuronal migration and wiring of the cerebral cortex. Nature Pub. Group 2014-09-05 /pmc/articles/PMC4164783/ /pubmed/25189171 http://dx.doi.org/10.1038/ncomms5826 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ye, Tao
Ip, Jacque P. K.
Fu, Amy K. Y.
Ip, Nancy Y.
Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex
title Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex
title_full Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex
title_fullStr Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex
title_full_unstemmed Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex
title_short Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex
title_sort cdk5-mediated phosphorylation of rapgef2 controls neuronal migration in the developing cerebral cortex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164783/
https://www.ncbi.nlm.nih.gov/pubmed/25189171
http://dx.doi.org/10.1038/ncomms5826
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