REGULATION OF NEUROGENESIS IN THE DROSOPHILA CNS

描述：在高等真核生物如人类中，某些组织 由一种特殊的细胞组成，称为干细胞。 干细胞分裂 自我更新的同时， 一种分化途径。 虽然很重要，但很少有 干细胞如何获得其身份或如何发挥其功能。 的 长期目标是了解管理开发的机制 以及干细胞谱系之一的中枢神经系统的功能 (CNS)果蝇Drosophila 在神经发生过程中，神经母细胞（NB）作为干细胞发挥作用， 通过不对称的有丝分裂来自我更新， 母细胞（GMCs） GMC虽然具有多能性，但不能自我更新; 相反，它不对称地分裂以产生两个不同的神经元。 在 在神经发生结束时，每半段被认为含有~320个不同的 和高度特化的神经元。 首席研究员选择了一个 典型的神经母细胞干细胞谱系，NB 4 -2谱系，产生 腹神经索中的运动神经元RP 2及其兄弟细胞RP 2-sib (the NB 4 -2-->GMC-1-> RP 2/同胞谱系），以解决如何 神经元前体细胞假设它们的身份以及它们如何经历 在神经发生中的不对称细胞分裂。 利用果蝇的力量 在遗传学方面，申请人已经通过遗传筛选确定了50多个新的 点突变和缺失突变，干扰发展的 NB 4 -2-->GMC-1-> RP 2/同胞谱系。 这些突变可以分为 引起：RP 2损失、RP 2增加、RP 2损失和增加， 分割缺陷、迁移缺陷和特殊类型的缺陷（例如， 仅来自CNS右侧的RP 2缺失）。 这些揭示了许多新的 神经母细胞干细胞谱系的阐述方面。 在这个提议中，主要研究者描述了实验， 进一步表征这些突变株系的子集。 这些实验 地址：A）GMC-1的非对称划分，B） GMC-1子代、RP 2和RP 2-同胞，以及C）在GMC-1子代、RP 2和RP 2-同胞期间的左右不对称性。 GMC-1身份的说明。 建议的研究包括：1）许多年轻的1，许多年轻的2和一个 先前鉴定的GMC-1特异性基因，mitimere，在 GMC-1的不对称分裂，2）信号分子果蝇Wnt 3， miti基因和GMC-1分裂失败的GMC分裂和RP 2/sib身份 规范，和3）单侧和左右不对称期间， RP 2/sib谱系的规范。 这些研究将有助于理解 在果蝇中枢神经系统中， 如在包括人类在内的其他真核生物中。

DESCRIPTION: In higher eukaryotic organisms such as humans, certain tissues consist of a special type of cells known as stem cells. Stem cells divide to self-renew and at the same time to generate a progeny that is committed to a differentiation pathway. Although of much importance, very little is known of how a stem cell acquires its identity or how it functions. The long term goal is to understand the mechanisms that govern the development and functioning of one of the stem cell lineages, the central nervous system (CNS), of the fruit fly Drosophila. During neurogenesis, a neuroblast (NB) functions as a stem cell and divides by asymmetric mitosis to self-renew and to produce a chain of ganglion mother cells (GMCs). A GMC, though pluripotential, does not self-renew; instead it divides asymmetrically to generate two distinct neurons. At the end of neurogenesis, each half segment is thought to contain ~320 distinct and highly specialized neurons. The principal investigator has selected a typical neuroblast stem cell lineage, the NB4-2 lineage, that generates the motoneuron, RP2, and its sibling cell (RP2-sib), in the ventral nerve chord (the NB4-2-->GMC-1->RP2/sib lineage), to address the problems of how neuronal precursor cells assume their identity and how they undergo asymmetric cell division during neurogenesis. Using the power of Drosophila genetics, the applicant has identified by genetic screens well over 50 new point and deletion mutations that perturb the development of the NB4-2-->GMC-1->RP2/sib lineage. These mutations can be categorized into those which cause: loss of RP2s, gain of RP2s, loss and gain of RP2s, division defects, migration defects and special types of defects (e.g., missing RP2s from only the right side of the CNS). These reveal many novel aspects of the elaboration of a neuroblast stem cell lineage. In this proposal, the principal investigator describes experiments to characterize further a subset of these mutant lines. These experiments address: A) the asymmetric division of the GMC-1, B) the specification of the GMC-1 progeny, RP2 and RP2-sib, and C) the left-right asymmetry during the specification of the GMC-1 identity. The proposed studies include: 1) many young ones 1, many young ones 2 and a previously identified GMC-1 specification gene, mitimere, during the asymmetric division of GMC-1, 2)the signaling molecule Drosophila Wnt3, the miti gene and failed GMC division in the GMC-1 division and RP2/sib identity specification, and 3) one sided and the left-right asymmetry during the specification of the RP2/sib lineage. These studies will help understand pathways that govern the lineage elaboration in the Drosophila CNS as well as in other eukaryotic organisms including humans.