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

We want our new neurons generated via neurogenesis to migrate to locations where they are needed. Ask your doctor exactly how to accomplish that. If they don't know ask what research they are creating to find out the answer. You can't let them do nothing, you are paying them, have them do some actual work.
http://dev.biologists.org/content/141/6/1404.short

1. Angeliki Louvi1,*,
2. Sayoko Nishimura1 and
3. Murat Günel1,2

+ Author Affiliations

1. ¹ Departments of Neurosurgery and Neurobiology, Yale Program on Neurogenetics, Yale School of Medicine, New Haven, CT 06520, USA.
2. ² Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.

1. ↵* 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.