The proposed studies will elucidate genes and their products (proteins) that are important for the development of brain and behavior. They focus on sexual differentiation of the structure and function of the song control system and associated regions in the telencephalon of zebra finches. Only males sing, and the brain areas and muscles that control song are larger in males than in females. In many vertebrates, the development of these types of male-biased differences in behavior and morphology is regulated by gonadal steroids. In zebra finches, some masculinization can be induced with estrogen treatment, but recent data suggest that at least the forebrain song control regions differentiate independent of gonadal secretions. Therefore, a screen will be conducted to discover genes that are expressed in a sexually dimorphic pattern in the telencephalon during development of the brain regions and singing behavior. Then, proteins regulating cytoarchitecture and/or specific functions (e.g., learning) will be targeted for more detailed investigation. Using this strategy, female-specific transcripts for neurocalcin, a calcium binding protein, were discovered. Experiments will clarify its role and that of calcium regulation in neural development. Other studies target the role of the estrogen-sensitive protein, brain derived neurotrophic factor (BDNF), in development of the song control nuclei and regions directly associated with them that are involved in song perception. The receptors for BDNF, which supports neuronal migration and survival, are present in these regions in both sexes when males are learning to sing, and perhaps females are learning the qualities of a good song. These studies will clarify the role of learning and the brain regions that are active during song perception in females (detailed information is already available for males), and will then test the hypothesis that BDNF modulates the development of these telencephalic structures and song-related functions in both sexes. The last set of studies examines whether mechanisms regulating development in the forebrain may apply to the motor nucleus and vocal organ muscles, and whether sexual differentiation is regulated by gonadal steroids in the hindbrain and periphery, similar to other dimorphic model systems.
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