This proposal will advance understanding of genetic regulators of neural stem cells in the brain through the study of a set of defined disorders characterised by brain malformations. These disorders have a signature indicating that neural stem cell function is defective, resulting in the distortion of the orderly layered structure of this organ. We hypothesise that the study of these conditions will point us to key genes and signalling pathways that regulate brain development by controlling how stem cells behave. The health impact of this knowledge lies in that all infants are born with substantial reserves of neural stem cells. They hold the potential to repair or replace damaged or dead neurons in children who have sustained brain insults. Fleshing out a genetic map of regulators of neural stem cells will facilitate the ability to mobilise this endogenous reserve of cells therapeutically in the context of neurological disease in young children.