Life and death decisions in Drosophila neural stem cells

 描述(由申请人提供)：单个细胞的生死决定对整个生物体的正常发育至关重要。虽然消除多余的细胞对于防止发育中的中枢神经系统肥大是必不可少的，但必要的细胞存活也同样重要。一些细胞是如何在一群相似的死亡细胞中存活下来的，这是一个鲜为人知的发育方面。果蝇提供了一个优秀的模型来研究发育中的中枢神经系统中的特定细胞是如何被选择来存活而其他细胞死亡的，这是因为关于神经发育的信息的广泛基础，可用来操纵发育中的动物的细胞凋亡的遗传方法，以及开放式筛选的简便性。我们已经证明，在果蝇的胚胎发生过程中，特定的神经干细胞可以通过细胞凋亡来消除。我们已经确定了对这一死亡很重要的调控和效应通路。在这里，我们建议从另一个角度来看待这种发育死亡：是什么保存了存活的干细胞子集？遗传学、组织学和分子方法将被用来定义在发育中的神经系统的背景下，负责单个干细胞存活的途径。这些研究将确定一些细胞在发育过程中用来避免细胞死亡的机制，并可能为人类疾病的治疗提供洞察力，如神经退化和癌症。

 DESCRIPTION (provided by applicant): The life or death decision of individual cells is critical for the proper development of the whole organism. While the elimination of superfluous cells is essential to prevent hypertrophy in the developing central nervous system, it is equally important that necessary cells survive. How some cells survive among a pool of similar cells that die is a poorly understood aspect of development. Drosophila provides an outstanding model to investigate how specific cells in the developing central nervous system are selected to survive while others die, due to the extensive foundation of information about neural development, the availability of genetic approaches to manipulate apoptosis in the developing animal, and the ease of open- ended screens. We have shown that specific neural stem cells are eliminated by apoptosis during embryogenesis in the fly. We have characterized the regulatory and effector pathways important for this death. Here, we propose to look at this developmental death from the other side: what preserves the subset of stem cells that survive? Genetic, histological and molecular approaches will be used to define the pathways responsible for the survival of individual stem cells in the context of the developing nervous system. These studies will determine the mechanisms that some cells use to avoid cell death in development and may provide insight into the treatment of human diseases such as neurodegeneration and cancer.