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Life and death decisions in Drosophila neural stem cells

果蝇神经干细胞的生死决定

基本信息

批准号：
8996736
负责人：
KRISTIN WHITE
金额：
$ 8.7万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8996736
关键词：
Abdomen Address Adult Animals Apoptosis Apoptosis Regulation Gene Apoptotic Back Biological Models Caspase Cell Death Cell Survival Cells Cessation of life Development Drosophila genus Embryo Embryonic Development Foundations Gene Activation Genes Genetic Genetic Transcription Health Homeobox Genes Hypertrophy Individual Learning Life Location Malignant Neoplasms Modeling Molecular Nerve Nerve Degeneration Nervous system structure Neuraxis Neurodegenerative Disorders Neuroglia Neurons Organism Pathway interactions Play Population Process Regulation Role Side Signal Pathway Signal Transduction Specific qualifier value Stem cells Survivors Techniques Whole Organism body system fly genetic approach human disease in vivo insight nerve stem cell nervous system development neuroblast neurodevelopment notch protein prevent sickling tool

项目摘要

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.

描述（由申请人提供）：单个细胞的生死决定对于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至关重要，但必要的细胞存活也同样重要。一些细胞如何在一群死亡的类似细胞中存活下来，这是发育的一个知之甚少的方面。果蝇提供了一个杰出的模型来研究如何在发育中的中枢神经系统中选择特定的细胞存活而其他细胞死亡，这是由于关于神经发育的广泛基础，遗传方法在发育中的动物中操纵细胞凋亡的可用性，以及开放式筛选的容易性。我们已经表明，特定的神经干细胞在胚胎发育过程中的苍蝇被淘汰的凋亡。我们已经确定了这种死亡的重要调控和效应途径。在这里，我们建议从另一个角度来看待这种发育性死亡：是什么保存了存活的干细胞亚群？遗传学、组织学和分子学方法将用于确定在发育中的神经系统中负责个体干细胞存活的途径。这些研究将确定一些细胞在发育过程中避免细胞死亡的机制，并可能为治疗人类疾病如神经变性和癌症提供见解。