Grant: Project Grant

The development of the nervous system is a highly complex process. During brain development, forms of stem cells called neural progenitors have two roles, first, they need to proliferate to ensure that the brain has the appropriate number of cells, and second, they need to differentiate to create the diverse array of cell types found in the brain. We identified a protein called DENND5A and our preliminary examination of this molecule indicates that it regulates decisions regarding proliferation versus differentiation in neural progenitors. We have now identified a cohort of patients who have a developmental disease called developmental and epileptic encephalopathy, caused by mutations in DENND5A. These children have severe intellectual impairment, epilepsy, and notable alterations in the structure of their brains. The studies described in this proposal will provide new insight into how alterations in DENND5A lead to this devastating neurological disease.