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 (March 2018) Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration. iScience, 1. pp. 35-48. ISSN 2589-0042

URL: https://www.ncbi.nlm.nih.gov/pubmed/29888765
DOI: 10.1016/j.isci.2018.01.004

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Optical Imaging Developmental Neuroscience Techniques in Neuroscience
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell migration
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell polarity
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Matt Covey
Date: 23 March 2018
Date Deposited: 16 Mar 2018 20:52
Last Modified: 14 Jun 2018 15:48
PMCID: PMC5993048
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36273

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