Small Rho-GTPases and cortical malformations

Rho-GTPases have been found to be crucial for cytoskeleton remodelling and cell polarity, as well as key players in directed cell migration in various tissues and organs, therefore becoming good candidates for involvement in neuronal migration disorders. We recently found that genetic deletion of the small GTPase RhoA in the developing mouse cerebral cortex results in three distinct cortical malformations: a defect in the proliferation of progenitor cells during development that leads to a bigger cerebral cortex in the adult mouse, a change in the morphology of radial glial cells that results in the formation of a subcortical band heterotopia (SBH, also called Double Cortex) and an increase in the speed of migrating newborn neurons. The latter, together with the aberrant radial glial shape, is likely to be the cause of cobblestone lissencephaly, where neurons protrude beyond layer I at the pial surface of the brain.