Format

Send to:

Choose Destination
See comment in PubMed Commons below
Development. 2014 Mar;141(6):1404-15. doi: 10.1242/dev.093526.

Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration.

Author information

  • 1Departments of Neurosurgery and Neurobiology, Yale Program on Neurogenetics, Yale School of Medicine, New Haven, CT 06520, USA.

Abstract

Loss of function of cerebral cavernous malformation 3 (CCM3) results in an autosomal dominant cerebrovascular disorder. Here, we uncover a developmental role for CCM3 in regulating neuronal migration in the neocortex. Using cell type-specific gene inactivation in mice, we show that CCM3 has both cell autonomous and cell non-autonomous functions in neural progenitors and is specifically required in radial glia and newly born pyramidal neurons migrating through the subventricular zone, but not in those migrating through the cortical plate. Loss of CCM3 function leads to RhoA activation, alterations in the actin and microtubule cytoskeleton affecting neuronal morphology, and abnormalities in laminar positioning of primarily late-born neurons, indicating CCM3 involvement in radial glia-dependent locomotion and possible interaction with the Cdk5/RhoA pathway. Thus, we identify a novel cytoplasmic regulator of neuronal migration and demonstrate that its inactivation in radial glia progenitors and nascent neurons produces severe malformations of cortical development.

KEYWORDS:

CCM3 (PDCD10); Cell autonomous function; Mouse; Nascent neurons; Neocortex; Radial glia

PMID:
24595293
[PubMed - indexed for MEDLINE]
PMCID:
PMC3943187
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk