Developmental genetics of neural stem cells

摘要 在果蝇神经索中，称为神经母细胞（NB）的神经元前体细胞经历了一个可变的过程， 自我更新的不对称分裂的数量。在发育过程中的某个时刻，这些细胞 变得静止，但稍后重新进入细胞周期，最终分裂成神经元，或经历细胞凋亡。没有人 知道这些前兆是测量经过的时间，还是计算在退出之前的分区数。 细胞周期在果蝇的神经系统中，NB的分裂潜力不同， 师. NB必须决定进入或退出细胞周期，但它们的读数是否是经过的时间或 细胞周期计数未知。此外，我们不知道该机制是否受 在细胞内或细胞外。这些都是很难回答的问题。通过检查不同类型的 NB，我们希望揭示调控细胞周期进入和退出的基因和机制， NB在发育过程中的分裂潜力。 在我们对前体细胞不对称分裂的遗传调控进行研究的过程中，我们分离出了一个 在神经索的许多谱系中引起前体细胞额外分裂的突变。我们 克隆了该基因，发现它是T-box蛋白家族的一员。这些蛋白质扮演重要角色 从发育到癌症我们对中线基因的研究使我们相信它调节前体细胞 进入和退出细胞周期。它似乎还通过与下列机构合作，作为机制的一部分发挥作用： 普洛斯彼罗因此，我们的具体目标是：1）确定Mid在细胞周期进入和退出中的作用， 神经干细胞，2）确定中期表达的调节，是否与系统有关 它调节或起源于它调节的细胞之外，以及3）确定Mid是否与 普洛斯彼罗指定前体细胞的分裂潜力。 前体细胞进入和退出细胞周期及其分裂潜能的调控是极其困难的 要研究的问题。无论这些调节机制是存在于细胞内还是细胞外， 测量经过的时间，或者是否存在决定/与细胞周期相互作用的计数机制 机械，都是未知数。我们的目标是利用一种强大的遗传学方法来探索这些问题。 系统绝不是这个建议只是中或专业为中心，这些球员的切入点，以解决 以上的生物学问题。

Abstract In the Drosophila nerve cord, neuronal precursor cells called neuroblasts (NBs) undergo a variable number of self-renewing asymmetric divisions. At some point during development, these cells either become quiescent but re-enter cell cycle later, terminally divide into neurons, or undergo apoptosis. No one knows whether these precursors measure elapsed time or count the number of divisions before exiting the cell-cycle. In the fly nervous system, NBs differ in their division potential--the number of times they undergo division. NBs must decide to enter or exit from the cell cycle, but whether their read out is the time elapsed or a cell cycle count is unknown. Additionally, we do not know whether the mechanism(s) is regulated from within the cell or extrinsic to the cell. These are difficult questions to address. By examining different types of NBs, we hope to reveal genes and mechanisms that regulate the cell cycle entry and exit, and the division potential of NBs during development. During the course of our work on genetic regulation of asymmetric division of precursors, we isolated a mutation that caused additional divisions of precursor cells in many lineages in the nerve cord. We cloned the gene and found that it is a member of the T-box protein family. These proteins play important roles from development to cancer. Our studies on this gene, midline, led us to believe that it regulates precursor cell entry and exit from the cell-cycle. It appears to also play a role as part of a mechanism by partnering with Prospero. Thus, our specific aims are: 1) Determine the role of Mid in the cell cycle entry and exit by neuronal stem cells, 2) Determine the regulation of mid-expression, whether it is linked to the system that it regulates or originates outside of the cells it regulates, and 3) Determine if Mid partners with Prospero to specify the division potential of precursor cells. The cell cycle entry and exit by precursors and the regulation of their division potential are exceedingly difficult problems to study. Whether these regulatory mechanisms reside within the cell or extrinsic to cells, do cells measure the time elapsed, or is there a counting mechanism that determines/interacts with the cell cycle machinery, are all unknowns. Our aims are focused on exploring these issues using a powerful genetic system. By no means is this proposal only Mid or Pros-centric, these players are entry points to tackle the above problems in biology.