9421697 Tobet This project is based on the central theme of understanding the sexual differentiation of brain structures. The preoptic area and anterior hypothalamus (POA/AH) comprise a region in the brain where there are many sex differences in cell distribution. Experiments will be conducted to examine how sex-specific subgroups begin to organize in the brain. Three basic questions will be addressed. First, studies will ask whether the cells in the POA/AH utilize cues from the orientation of glial guidance fibers for directed movement, and whether the patterns of migration change during development. Second, studies will ask where cells in the POA/AH come from, testing whether some cells migrate to the POA/AH after their birth in zones outside the POA/AH. Finally, the investigations will determine whether there are sex differences in cell migration. The experiments will utilize time-lapse live video microscopy to observe cell movement in vitro. Additionally, cells will be identified based on birthdate or the presence of specific proteins. Changes in the position of identified cells at different ages, relative to the orientation of glial guidance fibers, will be measured to provide a parallel index of cell migration. Information leading to discerning how the exquisitely complex preoptic area and hypothalamus develop and function normally will provide a new depth of understanding for a host of issues ranging from infertility to behavior.