The meninges as a signaling center in corticogenesis
University of California, San Francisco
The meninges (the area that immediately surrounds the brain) is now viewed as important in the development of the cerebral cortex, both as a physical barrier to migrating neuronal populations and as a source of developmental chemical signals. Recent evidence has suggested a role the meninges in the development of the cerebral cortex, and specifically, the involvement of the Foxc1 gene (a transcription factor found exclusively in the meninges) and TGF? (a growth factor). This study will use rodents as a model system to investigate the significance of meningeal Foxc1 and TGF? signaling in corticogenesis, and is designed to address three specific questions: (1) Why do mutations in Foxc1 lead to cortical dysgenesis? (2) Is there a relationship between Foxc1 and TGF? signaling in the meninges? (3) What is the importance of TGF? signaling in the meninges and in the developing cortex and in the adult cortex? A variety of histological and biochemical techniques will be used. What this means for people with autism: This proposal will point out important new mechanisms controlling prenatal and postnatal cortical development. In addition, it will help researchers better understand the types of cortical defects seen in a variety of neurodevelopmental disorders, including autism-spectrum disorders.