Genetic Studies of Cortex Structure and Development

University Of California San Francisco, San Francisco CA

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Abstract

DESCRIPTION (provided by applicant): The cerebral cortex is essential for higher cognitive functions of the mammalian brain. Anatomically distinct regions within the cortex are responsible for processing distinct functions. For instance, different domains of the cortex process different sensory inputs (i.e. vision, hearing, olfaction and somatosensation). Little is known about the developmental and genetic mechanisms that control parcellation of the cortex into these areas. I hypothesize that regionalization of the cerebral cortex is regulated by the expression of secreted molecules, such as Fgf8, by midline patterning centers of the embryonic telencephalon. These molecules may control regionalization through generating gradiential expression of transcription factors. The experiments proposed herein will explore the role of FGF8, and selected transcription factors whose expression appears to be controlled by FGF8, in regulating anteroposterior patterning of the cerebral cortex. These studies will have implications for understanding human disorders that range from gross malformations of the forebrain to dysfunction of individual subdivisions of the cerebral cortex.