http://dev.biologists.org/content/141/6/1404.short
+ Author Affiliations
- ↵* Author for correspondence (angeliki.louvi@yale.edu)
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.
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