Grant: Operating Grant

The neocortex is the region of the brain where higher cognitive functioning occurs, allowing us to perceive stimuli in the environment and have conscious thought. We study how the different cells that make up the neocortex are generated in the developing embryo. In particular, we focus on two genes (Neurog2/Ascl1) that together are responsible for generating the cellular diversity that characterizes this region of the brain. We have found that Neurog2/Ascl1 function like a switch - with the activation of one of these genes leading to the deactivation of the other. If the Neurog2/Ascl1 switch is disrupted, tipping the balance in favor of one gene versus the other, we observe a change in the ratios of the different cell types that make up the neocortex. This can have devastating consequences. For instance, we have found that a disruption of the Neurog2/Ascl1 switch occurs in some brain tumors. Our goal is to determine how Neurog2 and Ascl1 remain in their proper balance so that normal brain development can occur, and brain tumors do not arise.