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

Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration.
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DOI:
10.1016/j.isci.2018.01.004
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发表时间:
2018-03-23
期刊:
影响因子:
5.8
通讯作者:
Hatten ME
Hatten ME
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Govek EE;Wu Z;Acehan D;Molina H;Rivera K;Zhu X;Fang Y;Tessier-Lavigne M;Hatten ME

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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. Conditional deletion of Cdc42 in GCPs perturbs cerebellar cortical histogenesis Loss of Cdc42 in GCPs disrupts GCP neuron-glial junctions Cdc42 deficiency causes a loss of GCP polarity and slows their migration Phosphoproteomics reveals changes in cytoskeletal, adhesion, and polarity proteins Optical Imaging; Developmental Neuroscience; Techniques in Neuroscience
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