GENETIC AND MOLECULAR STUDIES OF NEUROGENESIS

描述（申请人的摘要逐字复制）：哺乳动物CNS 包含许多不同类型的神经元和神经胶质，每一种都发挥着特定的作用。 在调节运动、感知、认知和整体行为中的作用。是 了解不同的神经细胞类型 产生，因为它可以帮助我们认识到主要缺陷， 神经退行性疾病、神经系统癌症或行为 紊乱确定神经疾病的分子/遗传基础至关重要 来制定适当的治疗干预措施。我们用果蝇 作为理解神经多样性是如何产生的模型系统。最近 研究表明，果蝇和哺乳动物有着惊人的共同点， 在调节神经发生的机制中的保守性。因此，果蝇 研究是发现临床相关基因的有效手段。的 本文提出的研究的三个具体目标是：（1）识别和 表征基因，建立不同的神经细胞类型沿着 中枢神经系统的背腹轴哺乳动物运动神经元、中间神经元和感觉神经元 神经元从不同的区域沿着CNS的背腹轴沿着发育。 在果蝇中，沿着沿着神经细胞类型也有差异。 背腹轴，但很少有人知道的机制， 产生这些不同的神经命运。(2)识别和表征基因， 建立由单个干细胞产生的不同神经细胞类型。在 在哺乳动物中，单个大脑皮层干细胞可以产生神经元， 不同的层状命运;在果蝇中，单个神经干细胞（成神经细胞） 还产生了神经元和神经胶质的特征谱系， CNS内的形态和功能。我们想知道 干细胞可以产生多种神经元和神经胶质细胞类型。(3)表征 新发现的Sanpodo/Notch信号通路。Notch信号 信号通路是一种进化上保守的调节细胞命运的机制， 果蝇和哺乳动物;此外，Notch突变可导致白血病， 其他人类疾病。我们的数据表明，Sanpodo是一个肌动蛋白结合 蛋白质的许多刻缺蛋白依赖性信号事件内 果蝇CNS。我们计划进一步描述分子，遗传和 果蝇和人类Sanpodo基因在Notch调控中的生化功能 信号

DESCRIPTION(Applicant's abstract reproduced verbatim): The mammalian CNS contains many different types of neurons and glia, and each plays a specific role in regulating movement, perception, cognition, and overall behavior. It is clinically important to understand how different neural cell types are generated, because it may help us recognize the primary defect in neuro-degenerative diseases, cancers of the nervous system, or behavioral disorders. Defining the molecular/genetic basis of a neural disorder is vital for developing appropriate therapeutic interventions. We are using Drosophila as a model system for understanding how neural diversity is generated. Recent work has shown that Drosophila and mammals share a surprising degree of conservation in the mechanisms regulating neurogenesis. Thus, Drosophila research is an efficient means for uncovering clinically relevant genes. The three specific aims of the research proposed here are to: (1) Identify and characterize genes that establish different neural cell types along the dorsoventral axis of the CNS. Mammalian motoneurons, interneurons, and sensory neurons develop from distinct regions along the dorsoventral axis of the CNS. In Drosophila, there are also differences in the neural cell types along the dorsoventral axis, but very little is known about the mechanisms used to generate these distinct neural fates. (2) Identify and characterize genes that establish different neural cell types produced by individual stem cells. In mammals, a single cerebral cortical stem cell can generate neurons with distinct laminar fates; in Drosophila, a single neural stem cell (neuroblast) also generates a characteristic lineage of neurons and glia with diverse morphology and function within the CNS. We would like to understand how one stem cell can produce multiple, neuronal and glial cell types. (3) Characterize the newly discovered Sanpodo/Notch signaling pathway. The Notch signaling pathway is an evolutionarily conserved mechanism for modulating cell fate in Drosophila and mammals; in addition, Notch mutations can cause leukemia and other human diseases. Our data indicate that Sanpodo is an actin-binding protein necessary for many Notch-dependent signaling events within the Drosophila CNS. We plan to further characterize the molecular, genetic, and biochemical function of Drosophila and human Sanpodo genes in regulating Notch signaling.