Cell growth and proliferation control in neural stem cells

项目总结： 该研究项目的长期目标是了解营养来源的线索是如何整合的 通过细胞固有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，神经干细胞是自我 更新多能祖细胞。神经干细胞在调节大脑大小和 神经元多样性，因为这一群体在整个细胞周期中保持积极参与 发展。虽然人们已经做出了很多努力来识别基因和细胞 调节神经干细胞自我更新的信号通路，目前还不太清楚 外在因素，局部和全身，与内在神经干细胞因子相结合来控制 神经发生的时间和速度。在这里，使用果蝇的大脑作为一种基因上易驯服的 模型系统中，我们研究了营养来源的外在信号如何与细胞内在信号相结合 控制神经发生的时间和速度的程序。 在这个提案中，我们将调查(1)驱动不对称的机械 细胞分裂本身也在调节神经干细胞的生长和增殖方面发挥作用，(2)如何 营养调节神经干细胞的增殖，以及(3)一个特定的转录因子， 它是高度保守的，可以超越神经干细胞对营养的依赖需求 扩散。

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.