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Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration

CNS cortical histogenesis depends on polarity signaling pathways that regulate cell adhesion and motility. Here we report that conditional deletion of the Rho GTPase Cdc42 in cerebellar granule cell precursors (GCPs) results in abnormalities in cerebellar foliation revealed by iDISCO clearing method...

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Autores principales: Govek, Eve-Ellen, Wu, Zhuhao, Acehan, Devrim, Molina, Henrik, Rivera, Keith, Zhu, Xiaodong, Fang, Yin, Tessier-Lavigne, Marc, Hatten, Mary Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993048/
https://www.ncbi.nlm.nih.gov/pubmed/29888765
http://dx.doi.org/10.1016/j.isci.2018.01.004
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author Govek, Eve-Ellen
Wu, Zhuhao
Acehan, Devrim
Molina, Henrik
Rivera, Keith
Zhu, Xiaodong
Fang, Yin
Tessier-Lavigne, Marc
Hatten, Mary Elizabeth
author_facet Govek, Eve-Ellen
Wu, Zhuhao
Acehan, Devrim
Molina, Henrik
Rivera, Keith
Zhu, Xiaodong
Fang, Yin
Tessier-Lavigne, Marc
Hatten, Mary Elizabeth
author_sort Govek, Eve-Ellen
collection PubMed
description CNS cortical histogenesis depends on polarity signaling pathways that regulate cell adhesion and motility. Here we report that conditional deletion of the Rho GTPase Cdc42 in cerebellar granule cell precursors (GCPs) results in abnormalities in cerebellar foliation revealed by iDISCO clearing methodology, a loss of columnar organization of proliferating GCPs in the external germinal layer (EGL), disordered parallel fiber organization in the molecular layer (ML), and a failure to extend a leading process and form a neuron-glial junction during migration along Bergmann glia (BG). Notably, GCPs lacking Cdc42 had a multi-polar morphology and slowed migration rate. In addition, secondary defects occurred in BG development and organization, especially in the lateral cerebellar hemispheres. By phosphoproteomic analysis, affected Cdc42 targets included regulators of the cytoskeleton, cell adhesion and polarity. Thus, Cdc42 signaling pathways are critical regulators of GCP polarity and the formation of neuron-glial junctions during cerebellar development.
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spelling pubmed-59930482018-06-08 Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration Govek, Eve-Ellen Wu, Zhuhao Acehan, Devrim Molina, Henrik Rivera, Keith Zhu, Xiaodong Fang, Yin Tessier-Lavigne, Marc Hatten, Mary Elizabeth iScience Article CNS cortical histogenesis depends on polarity signaling pathways that regulate cell adhesion and motility. Here we report that conditional deletion of the Rho GTPase Cdc42 in cerebellar granule cell precursors (GCPs) results in abnormalities in cerebellar foliation revealed by iDISCO clearing methodology, a loss of columnar organization of proliferating GCPs in the external germinal layer (EGL), disordered parallel fiber organization in the molecular layer (ML), and a failure to extend a leading process and form a neuron-glial junction during migration along Bergmann glia (BG). Notably, GCPs lacking Cdc42 had a multi-polar morphology and slowed migration rate. In addition, secondary defects occurred in BG development and organization, especially in the lateral cerebellar hemispheres. By phosphoproteomic analysis, affected Cdc42 targets included regulators of the cytoskeleton, cell adhesion and polarity. Thus, Cdc42 signaling pathways are critical regulators of GCP polarity and the formation of neuron-glial junctions during cerebellar development. Elsevier 2018-03-08 /pmc/articles/PMC5993048/ /pubmed/29888765 http://dx.doi.org/10.1016/j.isci.2018.01.004 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Govek, Eve-Ellen
Wu, Zhuhao
Acehan, Devrim
Molina, Henrik
Rivera, Keith
Zhu, Xiaodong
Fang, Yin
Tessier-Lavigne, Marc
Hatten, Mary Elizabeth
Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration
title Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration
title_full Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration
title_fullStr Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration
title_full_unstemmed Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration
title_short Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration
title_sort cdc42 regulates neuronal polarity during cerebellar axon formation and glial-guided migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993048/
https://www.ncbi.nlm.nih.gov/pubmed/29888765
http://dx.doi.org/10.1016/j.isci.2018.01.004
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