Post-Embryonic Development of the Drosophila Brain

描述（由申请人提供）：脑发育涉及不同类型神经元的有序产生、定型神经元连接的建立、神经元投射的发育编程以及活性依赖性重塑。此外，像神经元一样，神经胶质细胞是大脑形成和功能不可或缺的。为了阐明大脑发育的分子机制，我们建议继续研究果蝇大脑的胚胎后发育，其中涉及各种有趣的发育现象，如功能神经回路中广泛的神经发生和胶质发生以及变态期间神经回路的大规模重塑。首先，我们将通过分离和表征更多的蘑菇体突变体来鉴定果蝇大脑胚胎后发育的各个方面所需的其他分子。其次，我们将研究是否以及如何众多不同的DSCAM分子协同和/或差异介导不同的细胞类型特异性神经元形态发生。第三，我们将开发新的MARCM技术，用于系统地同时检查胚胎后神经发生和胶质细胞生成。研究果蝇大脑的胚胎后发育有望为人类大脑中复杂的神经回路的形成提供新的线索。特别是，我们希望获得新的见解的分子机制，支配（1）不同类型的神经元的衍生共同的前体，（2）时序适当的神经元形态发生，（3）形成/延伸/指导/树枝状树突与轴突，（4）神经元投射的重塑，（5）不同细胞类型特异性神经元形态发生，（6）神经元-胶质细胞的相互作用。

DESCRIPTION (provided by applicant): Brain development involves orderly generation of distinct types of neurons, establishment of stereotyped neuronal connections, and developmentally programmed as well as activity-dependent remodeling of neuronal projections. In addition, like neurons, glial cells are integral to both formation and function of the brain. To elucidate the molecular mechanisms governing brain development, we propose to continue studying post-embryonic development of the Drosophila brain that involves various interesting developmental phenomena, such as extensive neurogenesis and gliogenesis in functional neural circuits and large-scale remodeling of neural circuits during metamorphosis. First, we will identify additional molecules required for various aspects of post-embryonic development of the Drosophila brain via isolating and characterizing more mushroom body mutants. Second, we will investigate whether and how numerous distinct DSCAM molecules operate collaboratively and/or differentially to mediate diverse cell type-specific neuronal morphogenesis. Third, we will develop novel MARCM technology for examining post-embryonic neurogenesis and gliogenesis systematically and simultaneously. Studying post-embryonic development of the Drosophila brain promises to shed new light on how complex neural circuits form in human brains. In particular, we expect to gain novel insights into the molecular mechanisms that govern (1) derivation of different types of neurons from common precursors, (2) chronologically appropriate neuronal morphogenesis, (3) formation/extension/guidance/arborization of dendrites versus axons, (4) remodeling of neuronal projections, (5) diverse cell type-specific neuronal morphogenesis, and (6) neuron-glial interactions.