REGULATION OF NEUROGENESIS IN THE DROSOPHILA CNS

描述：在高等真核生物中，如人类，某些组织 由一种称为干细胞的特殊类型的细胞组成。干细胞分裂 自我更新，同时产生承诺的后代 到分化的途径。虽然很重要，但很少是 已知干细胞如何获得其身份或如何发挥作用。这个 长期目标是了解管理发展的机制 以及干细胞谱系之一--中枢神经系统的功能 (CNS)，果蝇。 在神经发生过程中，神经母细胞(NB)起干细胞的作用，并将 通过不对称有丝分裂进行自我更新并产生神经节链 母细胞(GMC)。GMC虽然具有多重潜能，但不会自我更新； 相反，它不对称地分裂，产生两个不同的神经元。在 神经发生的结束，每半个片段被认为包含~320个不同的 和高度专门化的神经元。首席调查员选择了一名 典型的神经母细胞干细胞谱系，NB4-2谱系，产生 腹神经索中的运动神经元RP2及其兄弟细胞(RP2-SIB) (NB4-2--&gt；gmc-1-&gt；rp2/sib谱系)，以解决如何 神经前体细胞假定它们的身份以及它们是如何经历 神经发生过程中的不对称细胞分裂。利用果蝇的力量 遗传学，申请人已经通过基因筛查确定了远远超过50个新的 扰乱细胞生长发育的点突变和缺失突变 NB4-2--&gt；GMC-1-&gt；rp2/sib谱系。这些突变可以归类为 造成的原因：RP2s的损失，RP2s的获得，RP2s的损失和获得， 分割缺陷、迁移缺陷和特殊类型的缺陷(例如， 仅在CNS的右侧缺少RP2s)。这些揭示了许多小说 神经母细胞干细胞谱系的精细化方面。 在这份提案中，首席研究员描述了实验以 进一步描述这些突变系的一个子集。这些实验 地址：A)GMC-1的非对称划分，B)规范 GMC-1的后代、RP2和RP2-sib，以及C)左右不对称 GMC-1身份的规范。 建议的研究包括：1)许多年轻人1，许多年轻人2和 先前发现的GMC-1规范基因mitimere在 GMC-1的不对称分裂，2)信号分子果蝇WNT3， MITI基因与GMC-1分裂失败及RP2/sib的同源性 规范；3)单边和左右不对称 RP2/SIB谱系的规范。这些研究将有助于理解 果蝇中枢神经系统中支配谱系细化的途径也是如此 就像在包括人类在内的其他真核生物中一样。

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.