Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration
Summary: 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 cleari...
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doaj-0da546b96851415b8f4d8fff7ae605a92020-11-24T21:47:06ZengElsevieriScience2589-00422018-03-0113548Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided MigrationEve-Ellen Govek0Zhuhao Wu1Devrim Acehan2Henrik Molina3Keith Rivera4Xiaodong Zhu5Yin Fang6Marc Tessier-Lavigne7Mary Elizabeth Hatten8Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Brain Development and Repair, The Rockefeller University, New York, NY 10065, USAThe Rockefeller University Electron Microscopy Resource Center, The Rockefeller University, New York, NY 10065, USAThe Rockefeller University Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USAMass Spectrometry Shared Resource, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USALaboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Brain Development and Repair, The Rockefeller University, New York, NY 10065, USA; Stanford University, Palo Alto, CA 94305-2061, USALaboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065, USA; Corresponding authorSummary: 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. : Optical Imaging; Developmental Neuroscience; Techniques in Neuroscience Subject Areas: Optical Imaging, Developmental Neuroscience, Techniques in Neurosciencehttp://www.sciencedirect.com/science/article/pii/S258900421830004X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eve-Ellen Govek Zhuhao Wu Devrim Acehan Henrik Molina Keith Rivera Xiaodong Zhu Yin Fang Marc Tessier-Lavigne Mary Elizabeth Hatten |
spellingShingle |
Eve-Ellen Govek Zhuhao Wu Devrim Acehan Henrik Molina Keith Rivera Xiaodong Zhu Yin Fang Marc Tessier-Lavigne Mary Elizabeth Hatten Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration iScience |
author_facet |
Eve-Ellen Govek Zhuhao Wu Devrim Acehan Henrik Molina Keith Rivera Xiaodong Zhu Yin Fang Marc Tessier-Lavigne Mary Elizabeth Hatten |
author_sort |
Eve-Ellen Govek |
title |
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_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_sort |
cdc42 regulates neuronal polarity during cerebellar axon formation and glial-guided migration |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2018-03-01 |
description |
Summary: 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. : Optical Imaging; Developmental Neuroscience; Techniques in Neuroscience Subject Areas: Optical Imaging, Developmental Neuroscience, Techniques in Neuroscience |
url |
http://www.sciencedirect.com/science/article/pii/S258900421830004X |
work_keys_str_mv |
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1725899343654813696 |