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

ABSTRACT: Govek et al. demonstrate conditional loss of Cdc42 in cerebellar granule cell progenitors (GCPs) perturbs GCP polarity and impairs axon patterning, glial-guided migration, and cerebellar foliation. Phospho-proteomic analysis identified polarity and cytoskeletal proteins as affected targets in Cdc42 deficient GCPs.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: henrik molina

LAB HEAD: Mary E. Hatten

PROVIDER: PXD008148 | Pride | 2018-10-22

REPOSITORIES: Pride

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			Action	DRS
	MS162688QEp_eve_hatten_phostechmergedONLYPHOSbeforeimputation.txt	Txt
	MS162829LUM_eve_hatten_CDC42cKO-Dec16_phospho_a.raw	Raw
	MS162829LUM_eve_hatten_CDC42cKO-Dec16_phospho_b.raw	Raw
	MS162829LUM_eve_hatten_CDC42cKO-Jan1_phospho_a.raw	Raw
	MS162829LUM_eve_hatten_CDC42cKO-Jan1_phospho_b.raw	Raw

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

Govek Eve-Ellen EE Wu Zhuhao Z Acehan Devrim D Molina Henrik H Rivera Keith K Zhu Xiaodong X Fang Yin Y Tessier-Lavigne Marc M Hatten Mary Elizabeth ME

iScience 20180301

CNS cortical histogenesis depends on polarity signaling pathways that regulate cell adhesion and motility. Here we report that conditional deletion of the Rho GTPase <i>Cdc42</i> 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 ...[more]

PMID: 29888765

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Project description:Bergmann glia (BG) are important in the inward type of radial migration of cerebellar granule neurons (CGNs). However, details regarding the functions of Cdc42 and Rac in BG for radial migration of CGN are unknown. To examine the roles of Cdc42 and Rac in BG during cerebellar corticogenesis, mice with a single deletion of Cdc42 or Rac1 and those with double deletions of Cdc42 and Rac1 under control of the glial fibrillary acidic protein (GFAP) promoter: GFAP-Cre;Cdc42flox/flox (Cdc42-KO), GFAP–Cre;Rac1flox/flox (Rac1-KO), and GFAP-Cre;Cdc42 flox/flox;Rac1flox/flox (Cdc42/Rac1-DKO) mice, were generated. Both Cdc42-KO and Rac1-KO mice, but more obviously Cdc42-KO mice, had disturbed alignment of BG in the Purkinje cell layer (PCL). We found that Cdc42-KO, but not Rac1-KO, induced impaired radial migration of CGNs in the late phase of radial migration, leading to retention of CGNs in the inferior half of the molecular layer (ML). Cdc42-KO, but not Rac1-KO, mice also showed aberrantly aligned Purkinje cells (PCs). These phenotypes were exacerbated in Cdc42/Rac1-DKO mice. Alignment of BG radial fibers in the ML and BG endfeet at the pial surface of the cerebellum evaluated by GFAP staining was disturbed and weak in Cdc42/Rac1-DKO mice, respectively. Our data indicate that that Cdc42 and Rac, but predominantly Cdc42, in BG play important roles during the late phase of radial migration of CGNs. We also report here that Cdc42 is involved in gliophilic migration of CGNs, in contrast to Rac, which is more closely connected to regulating neurophilic migration.

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