Post-Embryonic Development of the Drosophila Brain

描述(申请人提供)：大脑发育需要有秩序的 产生无数不同类型的神经元，建立复合体 细胞间的连接和神经元突起的重塑 经验。为了研究大脑的分子机制 发育和可塑性，我想研究一个微小的幼虫大脑是如何 果蝇长得很大，进化成了一种更复杂的 在其神经回路大规模重塑后的大脑。了解如何 神经前体细胞可以在功能性神经系统中分化出不同类型的神经元。 大脑对于人类大脑未来的细胞替代疗法非常重要。 识别参与神经元突起重塑的分子可能 进一步阐明如何操纵我们大脑中的神经回路。我提议 果蝇中枢神经系统胚胎后发育的研究 从三个不同的角度。在第一个目标中，我将进行广泛的遗传 筛选确定蘑菇体发育所需的基因 形成昆虫学习记忆中心。蘑菇体神经元是 将创建随机突变的纯合子，并在ELSE中进行分析 野生型生物。这种方法导致了对 超阿司匹林(USP)，编码蜕皮激素受体的一个亚单位，作为一种 神经元过程中幼虫特异性突起修剪的必需基因 改建。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后的各个方面 神经元发育。将使用马赛克方法来检查USP在 胚胎后神经发生和形态分化 成体特有的神经元。在第三个目标中，我想要识别分子 专用于不同类型神经元及其前体的标志物 在胚胎后期发育期间，这将极大地促进未来 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.