Post-Embryonic Development of the Drosophila Brain

描述（由申请人提供）：大脑发育需要有序的 产生许多不同类型的神经元，建立复杂的 细胞-细胞连接，以及神经元过程的重塑， 体验.为了研究大脑的分子机制 发展和可塑性，我想研究如何一个微小的幼虫的大脑， 果蝇会长得很大，进化成一种更复杂的 在大规模重塑其神经回路后的大脑。了解如何 神经元祖细胞可以产生不同类型的神经元， 对于人类大脑中未来的细胞替代疗法来说很重要。 鉴定参与神经元过程重塑的分子， 进一步阐明如何操纵我们大脑中的神经回路。我建议 研究果蝇中枢神经系统的胚胎后发育 从三个不同的角度在第一个目标，我将进行广泛的遗传 筛选出蘑菇体发育所需的基因， 形成昆虫的学习和记忆中心。蘑菇体神经元 随机突变的纯合子将被创建，并在其他情况下进行分析。 野生型生物。这一方法导致了对 超气门（USP），其编码蜕皮激素受体的一个亚基，作为一种 在神经元发育过程中修剪幼虫特异性过程的必需基因 重塑在第二个目标中，我将直接测试假设， 昆虫激素蜕皮激素协调胚胎发育后的各个方面， 神经元发育马赛克方法将用于检查USP在以下方面的作用： 胚胎后神经发生和形态分化 成人特有的神经元在第三个目标中，我想确定分子 对不同类型的神经元及其前体具有特异性的标记物 在胚胎后的发育过程中，这将极大地促进未来的 复杂神经系统的分子遗传学研究。

DESCRIPTION (provided by applicant): Brain development requires the orderly generation of numerous distinct types of neurons, establishment of complex cell-cell connections, and remodeling of neuronal processes in response to experience. In order to investigate the molecular mechanisms underlying brain development and plasticity, I would like to study how a tiny larval brain of the Drosophila grows enormously and evolves into a much more sophisticated brain after large-scale remodeling of its neural circuits. Understanding how neuronal progenitors can give rise to distinct types of neurons in a functional brain is important for future cell replacement therapies in human brains. Identification of molecules involved in remodeling of neuronal processes may further elucidate how to manipulate neural circuits in our brains. I propose to study the post-embryonic development of the Drosophila central nervous system from three distinct angles. In the first aim, I will conduct extensive genetic screens to identify genes required for development of the mushroom bodies that form the insect learning and memory center. Mushroom body neurons that are homozygous for a random mutation will be created and analyzed in otherwise wild-type organisms. This approach has led to identification of the ultraspiracle (usp), which encodes one subunit of the ecdysone receptor, as an essential gene for pruning of larval-specific processes during neuronal remodeling. In the second aim, I will directly test the hypothesis that the insect hormone ecdysone orchestrates various aspects of the post-embryonic neuronal development. Mosaic approaches will be used to examine roles of USP in both post-embryonic neurogenesis and morphological differentiation of adult-specific neurons. In the third aim, I would like to identify molecular markers that are specific for distinct types of neurons and their precursors during the post-embryonic development, which will greatly facilitate future molecular genetic studies in the complex nervous system.