Molecular Genetics of Stem Cell in Drosophila

果蝇干细胞的分子遗传学

• 批准号: 7684198
• 负责人: KRISHNA MOORTHI BHAT
• 金额: $ 20.93万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7684198
• 关键词: Animal Model; Area; Automobile Driving; Biological; Biological Models; Boxing; Cell Lineage; Cell division; Cells; Chromatin; Commit; Complex; Cyclin E; Drosophila genus; Embryo; Eukaryota; Family; Ganglia; Genes; Genetic; Genetic Screening; Goals; Grant; Laboratories; Mitosis; Mitotic; Modeling; Molecular Genetics; Mothers; Mutation; Myxoid cyst; Names; Nerve; Nervous system structure; Neuralized-like Protein; Neuraxis; Neurons; Organism; Pathway interactions; Polycomb; Principal Investigator; Proteins; Regulation; Role; Series; Stem cells; Testing; Time; Tissues; Up-Regulation; Work; base; cell type; chromatin protein; daughter cell; ganglion cell; in vitro activity; loss of function; loss of function mutation; member; nerve stem cell; neural precursor cell; neuroblast; neurogenesis; precursor cell; programs; response; self-renewal; stem cell division; ubiquitin ligase; ubiquitin-protein ligase

DESCRIPTION (provided by applicant): In higher eukaryotes, 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. In Drosophila, the primary neuronal precursor cells (Neuroblasts, NB) function as stem cells and divide by self-renewing asymmetric mitosis. During neurogenesis, a NB self-renews and also produces a chain of ganglion mother cells (GMCs). A GMC is bipotential, it does not self-renew but divides asymmetrically to generate two distinct post-mitotic neurons. Thus, from -30 NBs in a given hemisegment, -320 distinct neurons are generated. This indicates that the ability of NBs to function as stem cells and the ability of NBs and GMCs to divide by asymmetric mitosis is crucial in generating a large number of neurons from a few precursor cells. Our long-term goal aims to explore the genetic regulation of self-renewing stem cell type of asymmetric divisions using the Drosophila CNS as our model system. In order to study the problem of self-renewing and terminal asymmetric divisions, we have selected several different CNS lineages: MP2, NB7-3, GMC-1->RP2/sib, and GMC-1->aCC/pCC lineages. During the past several years, we have identified through genetic screens mutations that show self-renewing and terminal asymmetric division in one or more of these lineages. In this grant we propose to further study these mutations. Thus, our specific aims include: (1) To investigate the role of Midline in inhibiting the self- renewing asymmetric division potential of neural precursor cells, and, 2) To determine how Neuralized-like inhibits the self-renewing asymmetric division potential of precursor cells, and 3) To determine the role of Polycomb, a chromatin re-modeling protein, in the asymmetric division of GMCs. These studies will help understand pathways that govern the self-renewing and terminal asymmetric division of precursor cells in multi-cellular organisms.

描述（由申请人提供）：在高等真核生物中，某些组织由称为干细胞的特殊类型的细胞组成。干细胞分裂以自我更新，同时产生致力于分化途径的后代。虽然非常重要，但对干细胞如何获得其身份或如何发挥功能知之甚少。在果蝇中，原代神经元前体细胞（成神经细胞，NB）具有干细胞的功能，并通过自我更新的不对称有丝分裂进行分裂。在神经发生期间，NB自我更新并且还产生神经节母细胞（GMC）链。GMC是双能的，它不自我更新，但不对称地分裂以产生两个不同的有丝分裂后神经元。因此，从给定半节段中的约30个NB，产生约320个不同的神经元。这表明NB作为干细胞发挥功能的能力以及NB和GMC通过不对称有丝分裂分裂的能力在从少数前体细胞产生大量神经元中至关重要。我们的长期目标是以果蝇中枢神经系统为模型系统，探索自我更新干细胞类型的不对称分裂的遗传调控。为了研究自我更新和末端不对称分裂的问题，我们选择了几个不同的CNS谱系：MP2、NB 7 -3、GMC-1-> RP 2/sib和GMC-1->aCC/pCC谱系。在过去的几年中，我们已经确定了通过基因筛选突变，显示自我更新和终端不对称分裂在一个或多个这些谱系。在这项资助中，我们建议进一步研究这些突变。因此，我们的具体目标包括：（1）研究Midline在抑制神经前体细胞的自我更新不对称分裂潜能中的作用，和，2）确定Neuralized-like如何抑制前体细胞的自我更新不对称分裂潜能，和3）确定Polycomb（染色质重塑蛋白）在GMC的不对称分裂中的作用。这些研究将有助于了解多细胞生物体中前体细胞自我更新和末端不对称分裂的调控途径。