DESCRIPTION (applicant's abstract): The long term goal of the proposed studies is to understand the molecular signals that initiate sexually dimorphic development of the brain, and lead to sex differences in behavior. A great deal of experimental evidence indicates that one of these signals is testosterone, secreted by the testes before or after birth, which acts directly or indirectly on the brain of males to cause masculine patterns of neural development. However, some sex differences in the brain are not induced by gonadal steroids, and the proposed studies test an alternative hypothesis, that genes on the sex chromosomes are differentially expressed in male and female brain and lead, via non- hormonal mechanisms, to sex differences in neural development and behavior. To analyze this hypothesis, we will measure various parameters of brain structure and function, and of behavior, in male and female mice of selected genotypes that carry different numbers of X and Y chromosomes, or different portion of the sex chromosomes in varying numbers. The parameters to be measured are known sexual dimorphisms in brain structure and function and behavior. The proposed studies will determine if any genes on the Y or X chromosome contribute to sex differences in neural and behavioral development, and will narrow down the location of these genes to specific regions of the sex chromosomes. The proposed research will contribute significantly to an understanding of the principles of sexual differentiation of the brain. At issue are the molecular mechanisms by which male and female brains differ, which is highly relevant to biological basis of abnormalities of sexual differentiation, and to the explanation of sex differences in psychiatric and neural disease (e.g., Alzheimer's Disease and Multiple Sclerosis).