The frontal cortex arguably houses the most important set of integrators of cognition, emotion and motor control in the mammalian brain. Therefore, understanding the genetic mechanisms that control development of the prefrontal and motor cortex have clear ramifications for understanding neuropsychiatric disorders. I hypothesize that one can gain fundamental insights into this subject through the analysis of how Fgf8 signaling regulates development of the telencephalon. Fgf8 signaling is now firmly established as a central mechanism that controls molecular regionalization and morphogenesis of the rostral telencephalon, including the frontal neocortex. In this grant application I describe experiments aimed at testing the hypothesis that analysis of mice bearing mutations in Fgf agonists (Fgf8, 15 and 17), FGF antagonists (Sproutyl and 2) and transcription factors that are regulated by Fgf8 (COUPTF1 and Emx2) will elucidate mechanisms that regulate the size, nature and function of the frontal cortex.
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