Grant: Project 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. The original dogma was that new neurons could not be generated after embryonic development since there were no stem cells to replace lost neurons. However, more recent studies have identified a pool of neural stem cells that reside in the adult brain. Moreover, it has been found that these stem cells are first born in the embryonic period, persisting in an inactive state until adulthood. We have been studying how neural stem cells decide to be inactive, or divide and differentiate into neurons in the embryonic brain. These studies have focused on proneural genes, which we found mark a pool of slow-dividing neural stem cells in the embryo and adult. We now try to understand how the proneural genes control whether neural stem cells remain inactive, divide or differentiate. We have three aims in this study. In the first aim we examine how slow-dividing stem cells that express these proneural genes respond to a brain injury, and trace their embryonic progeny. In the second aim, we ask how these proneural genes can be manipulated to induce neural stem cells to produce new neurons in development and after brain injury. In the third aim, we begin to model the roles of these proneural genes in a primate system, using monkey tissue and generating brain organoids from human cells as a surrogate model system. These studies are important because re-invigoration of these dormant stem cells by manipulating the proneural genes may aid brain repair.