It has been recently reported that some individuals with autism show premature brain overgrowth early in development. Recent studies have demonstrated that brain overgrowth can be caused by the interaction of environmental factors such as maternal inflammatory response (MIR) with genetic susceptibility during periods of vulnerability in fetal development. This research seeks to understand mechanisms of MIR-induced macrocephaly in autism spectrum disorder (ASD). One mechanism by which genes and environment might interact in maternal inflammatory response is through the production of reactive oxygen species (ROS). While it is well known that high levels of ROS are toxic to cells, the effects of low levels of ROS are unknown. Maternal and embryonic ROS levels can be influenced by many environmental factors including viral infection and allergic/immune disorders which have also been positively associated with macrocephaly. This lab has previously shown that low levels of ROS produced by NADPH oxidases (NOX) enhance neural stem cell self-renewal, at least in part due to disruption of PTEN function. Here, they will determine whether there is a pathogenic link between NOX-generated ROS and brain size in a rodent model.