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Cell growth and proliferation control in neural stem cells

神经干细胞的细胞生长和增殖控制

基本信息

批准号：
9327030
负责人：
Sarah Elizabeth Siegrist
金额：
$ 32.35万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9327030
关键词：
1-Phosphatidylinositol 3-Kinase Adult Age Age-associated memory impairment Alpha Cell Anabolism Anencephaly Animals Apical Binding Biological Models Brain Cell Cycle Cell Cycle Regulation Cell Lineage Cell Polarity Cell Proliferation Cell division Cells Cognition Congenital Abnormality Couples Cues Defect Development Drosophila genus Elderly Embryonic Development Ensure Experimental Models G-substrate GTP-Binding Proteins Genes Genetic Transcription Goals Growth Heterotrimeric GTP-Binding Proteins Hormones Individual Insulin Insulin Receptor Intrinsic factor Knowledge Larva Lead Link Location Mammals Mediating Methods Microcephaly Mitosis Modeling Molecular Multipotent Stem Cells Mushroom Bodies Neurons Nutrient Organism Pathway interactions Peptides Physiology Play Population Proliferating Proteins Receptor Signaling Regulation Research Research Project Grants Role Signal Pathway Signal Transduction Stem cells Structure Subgroup Testing Time Transcriptional Regulation brain circuitry brain size cell growth feeding insight macromolecule mutant nerve stem cell neuroblast neurogenesis nutrition overexpression premature programs relating to nervous system response self-renewal stem cell division transcription factor

项目摘要

Project Summary: The long term goal of this research project is to understand how nutrient derived cues integrate with cell intrinsic programs to control timing and rate of neurogenesis. All neurons within our brains are generated from the asymmetric cell divisions of neural stem cells, which are self- renewing multi-potent progenitors. Neural stem cells play a key role in regulating brain size and neuronal diversity, as this population remains actively engaged in the cell cycle throughout development. While much effort has been geared towards identifying genes and the cell signaling pathways that regulate neural stem cell self-renewal, less is known about how extrinsic factors, local and systemic, integrate with intrinsic neural stem cell factors to control timing and rate of neurogenesis. Here, using the Drosophila brain as a genetically tractable model system, we investigate how nutrient derived extrinsic signals integrate with cell intrinsic programs to control timing and rate of neurogenesis. In this proposal, we will investigate (1) whether the machinery that drives asymmetric cell division itself also play a role in regulating neural stem cell growth and proliferation, (2) how nutrition regulates neural stem cell proliferation, and (3) how a particular transcription factor, which is highly conserved, can override nutrient-dependent requirements for neural stem cell proliferation.

项目概要：这个研究项目的长期目标是了解营养来源的线索如何整合用细胞内在的程序来控制神经发生的时间和速度。我们大脑中的所有神经元大脑是由神经干细胞的不对称细胞分裂产生的，更新多能祖细胞。神经干细胞在调节大脑大小方面起着关键作用，神经元的多样性，因为这个群体始终积极参与细胞周期发展虽然许多努力都是为了识别基因和细胞，信号通路调节神经干细胞的自我更新，很少有人知道如何外源性因素，局部和全身，与内在的神经干细胞因子整合，以控制神经发生的时间和速率。在这里，使用果蝇的大脑作为一个遗传上易于处理的模型系统中，我们研究了营养来源的外源信号如何与细胞内源信号整合，程序来控制神经发生的时间和速度。在这个建议中，我们将研究（1）驱动不对称的机制是否细胞分裂本身也在调节神经干细胞的生长和增殖中发挥作用，（2）如何营养调节神经干细胞增殖，以及（3）特定的转录因子，它是高度保守的，可以超越神经干细胞对营养的依赖性需求，增殖