Sex Differences in Brain and Behavior Development

描述(申请人提供)：这项研究的重点是斑马雀鸣叫系统的性别分化，将阐明对神经系统、肌肉和行为发育至关重要的基因及其产物。只有男性唱歌，控制歌唱的大脑区域和肌肉比女性大。在许多脊椎动物中，这些类型的二形性的发展是由性腺类固醇调节的。在斑马雀中，雌激素治疗可以改变分化，但最近的数据表明，前脑歌曲控制区的分化不依赖性腺分泌。因此，在形态和歌唱行为的发育过程中，将对端脑中以性别二态模式表达的基因进行筛选。然后，将更详细地研究调节细胞结构和/或特定功能(例如，学习)的基因/蛋白质。利用这一策略，发现了女性特有的神经钙素转录本。实验将阐明它们的作用以及钙调节在神经发育中的作用。其他研究的目标是雌激素敏感蛋白、脑源性神经营养因子(BDNF)在歌曲控制核团和涉及歌曲感知的区域的发育中的作用。这些研究将阐明学习的重要性和女性在歌曲感知过程中活跃的大脑区域(男性已有详细信息)，然后将检验BDNF调节这些端脑结构和与歌曲相关的功能在两性中的发展的假设。最后，将确定前脑调节发育的机制是否适用于运动核和发声器官肌肉，以及这一水平的性别分化是否与其他二态模型系统类似，正常情况下是由性腺类固醇介导的。这一独立科学家奖的候选人是密歇根州立大学的副教授，她的教学负担和服务义务都很大。该奖项将为她提供时间来(1)加强她在分子技术方面的培训(与其他科学家合作提出的那些，以及对未来实验有用的新技术)；(2)拓宽她的解剖学专长；(3)更直接地为拟议的研究做出贡献，这将提高进展速度；以及(4)通过与她所在领域的领导者建立一系列研讨会，加强她日益增长的神经内分泌小组的合作和知名度，以及对学生和博士后的培训。

DESCRIPTION (provided by applicant): The studies, focusing on sexual differentiation of the song system in zebra finches, will elucidate genes and their products important for nervous system, muscle and behavioral development. Only males sing, and the brain areas and muscles that control song are larger than in females. In many vertebrates, development of these types of dimorphisms is regulated by gonadal steroids. In zebra finches, differentiation can be altered with estrogen treatment, but recent data suggest that the forebrain song control regions differentiate independent of gonadal secretions. Therefore, a screen will be conducted for genes expressed in a sexually dimorphic pattern in the telencephalon during development of morphology and singing behavior. Then, genes/proteins regulating cytoarchitecture and/or specific functions (e.g., learning) will be investigated in more detail. Using this strategy, female-specific transcripts for neurocalcin were discovered. Experiments will clarify their 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 involved in song perception. These studies will clarify the importance 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 development of these telencephalic structures and song-related functions in both sexes. Finally, it will be determined whether mechanisms regulating development in the forebrain apply to the motor nucleus and vocal organ muscles, and whether sexual differentiation at this level is normally mediated by gonadal steroids, similar to other dimorphic model systems. The candidate for this Independent Scientist Award is an associate professor at Michigan State University, and her teaching load and service obligations are substantial. The award would provide her time to (1) enhance her training in molecular techniques (those proposed in collaboration with other scientists, and new ones useful for future experiments); (2) broaden her anatomical expertise; (3) contribute to the proposed studies more directly, which will increase the rate of progress; and (4) enhance collaborations and visibility of her growing neuroendocrine group, as well as training of students and postdocs, by establishing a seminar series with leaders in her field.