Glial remodeling in Drosophila: proliferation, membrane outgrowth and nerve enshe

描述（申请人提供）：神经胶质细胞是人类神经系统中最丰富的细胞，约占人脑的90%。在成熟的神经系统中，胶质细胞在支持和维持功能中的作用已经得到了很好的证实。最近，神经胶质细胞的新角色出现了，它对神经系统的发展至关重要，对大脑功能和信息处理有影响。我们研究了包裹果蝇周围神经的胶质细胞。它们在胚胎中产生，在幼虫和后来的蛹中经历一轮又一轮的增殖，这时成虫的神经系统正在重组。果蝇胚胎中的每条神经都被3层神经胶质包裹着——最里面的包裹神经胶质层、亚神经膜层、神经膜层和被称为神经板的细胞外基质层。随着幼虫体型的增长，神经变长。神经鞘的维持是靠最外层的增生，而内层则增加其延伸。本提案的研究集中在蛹期，此时神经系统经历了剧烈的重组，以适应新的身体形态和行为。这种重组的一个方面是融合5对腹后神经形成末梢神经干（TNT）。我们的研究旨在了解（胚胎来源的）外周胶质细胞在TNT形成的背景下的重塑。我们将研究具有独特功能的三种不同的胶质细胞类型如何在数量和结构上增加以允许神经融合，同时保持血脑屏障完整。单独的神经胶质层也将被操纵以揭示它们对神经重组的贡献，这将导致成人特有的模式。我们希望揭示胚胎期、幼虫期和蛹期神经胶质形态发生的异同，因为它关系到神经系统的结构和功能。我们的研究将有助于更好地理解神经胶质瘤等人类疾病。

DESCRIPTION (provided by applicant): Glia are the most abundant cells of the human nervous system, and make up about 90% of the human brain. The role of glia in support and maintenance functions in the mature nervous system is well established. More recently, new roles for glia have emerged that are central to development of the nervous system, that has a bearing on brain function and information processing. We study glia which ensheath peripheral nerves in the fruit-fly. They are generated in the embryo and undergo bouts of proliferation in the larva and later in the pupa when the adult nervous system is being re-organized. Each nerve in the Drosophila embryo is ensheathed by 3 glial layers- an innermost wrapping glial layer, the sub-perineurial layer, the perineurial layer and an extracellular matrix layer called the neural lamella. As the larva grows in size, the nerves become longer. Maintenance of nerve ensheathment occurs by proliferation of the most external layer, while the inner 2 layers increase their extensions. Studies in this proposal focus on the pupal phase when the nervous system undergoes a drastic re-organization to accommodate a new body form and behaviors. One aspect of this re-organization is the fusion of 5 pairs of posterior abdominal nerves to form a terminal nerve trunk (TNT). Our studies are aimed at understanding remodeling of (embryonically derived) peripheral glia in the context of TNT formation. We will examine how 3 distinct glial cell-types with unique functions increase in number and restructure to allow nerve fusion while keeping the blood-brain barrier intact. Individual glial layers will also be manipulatd to uncover their contribution to nerve re- organization, which results in the adult-specific patter. We hope to uncover similarities/differences between the embryonic, larval and pupal stages in regard to glial morphogenesis as it relates to nervous system structure and function. Our studies will contribute to a better understanding of human conditions such as gliomas. PUBLIC HEALTH RELEVANCE: Glial cells are the most common cell-type in the nervous system and are essential to the structure and functioning of the nervous system. We study glia which ensheath peripheral nerves in the fruit-fly. They are generated in the embryo and undergo bouts of proliferation in the larva and later in the pupa when the adult nervous system is being re- organized. Our studies will examine how 3 distinct glial cell-types with unique functions increase in number and begin the process of enstheathing the segmental nerves. We hope to uncover similarities/differences between the embryonic, larval and pupal stages in regard to glial morphogenesis as it relates to nervous system and structure. Our studies will contribute to a better understanding of human conditions such as gliomas.