Grant: Project Grant

The outermost layer of the brain, just below the skull, is the cerebral cortex. The cerebral cortex is the seat of our intellect, and in healthy people it has many deep folds. In unfortunate cases, however, a genetic mutation causes a loss of these folds, a disease known as "smooth brain," or lissencephaly. The mutations occur in a protein called doublecortin (DCX). DCX works inside of brain cells, or neurons, to control where neurons are located in the brain and how neurons connect to one another. In humans with DCX mutations, neurons are not located properly in the brain and do not make correct connections, causing mental retardation and epilepsy. We know that DCX works by controlling the shape of the "cytoskeleton," a scaffolding system inside of cells that give them structure, much like the scaffolds used at construction sites. The goal of this grant is to understand precisely how DCX controls the shape of the cytoskeleton and to explain why DCX mutations cause disease.