The proposed studies have two long-term goals: (1) to understand the molecular signals that initiate sexually dimorphic development of the brain, and (2) to understand the forces that balance and regulate X chromosome gene expression in brain. Most sex differences in the brain are currently attributed to the action of gonadal steroid hormones. This concept needs to be modified, however, based on recent information suggesting that some X chromosome genes are expressed at a higher level in the female brain and may contribute to sex differences in brain development. The present application aims to determine whether a group of brain-related X-linked genes are sexually dimorphic in their expression, and to determine if the sex differences in expression are predicted by the X-inactivation status of each gene measured in the brain itself. The proposed research will contribute significantly to an understanding of the principles of sexual differentiation of the brain, including the molecular mechanisms by which male and female brains differ. The research will also help explain abnormalities of sexual differentiation, as well as sex differences in neurological and psychiatric disease (e.g., mental retardation). ? ?
