Molecular Genetics of Stem Cell in Drosophila

果蝇干细胞的分子遗传学

基本信息

批准号：
7248249
负责人：
KRISHNA MOORTHI BHAT
金额：
$ 21.14万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7248249
关键词：
Animal Model Area Automobile Driving Biological Biological Models Boxing Cell Lineage Cell division Cells Chromatin Commit Complex Cyclin E Down-Regulation Drosophila genus Embryo Equilibrium Eukaryota Eukaryotic Cell Family Ganglia Gene Proteins Genetic Genetic Screening Goals Grant In Vitro Informal Social Control Laboratories Lead MCC protocol Mitosis Mitotic Modeling Molecular Genetics Mothers Mutation Myxoid cyst Names Nerve Nervous system structure Neuralized-like Protein Neuraxis Neurons Numbers Organism Pathway interactions Polycomb Process Proteins Regulation Role Series Stem cells Time Tissues Transcriptional Activation Up-Regulation Vertebrates Work base cell type chromatin protein daughter cell ganglion cell gene conservation insight loss of function loss of function mutation member nerve stem cell neuroblast neurogenesis precursor cell relating to nervous system response ubiquitin ligase

项目摘要

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，某些组织由一种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。尽管干细胞非常重要，但人们对干细胞如何获得其身份或如何发挥作用知之甚少。在果蝇中，初级神经元前体细胞（神经母细胞，NB）起到干细胞的作用，并通过自我更新的不对称有丝分裂进行分裂。在神经发生过程中，NB 会自我更新，并产生一系列神经节母细胞 (GMC)。 GMC 是双电位的，它不会自我更新，但会不对称地分裂以产生两个不同的有丝分裂后神经元。因此，从给定半段中的 -30 个 NB 中，生成 -320 个不同的神经元。这表明NB作为干细胞发挥作用的能力以及NB和GMC通过不对称有丝分裂进行分裂的能力对于从少数前体细胞产生大量神经元至关重要。我们的长期目标是使用果蝇中枢神经系统作为我们的模型系统，探索不对称分裂的自我更新干细胞类型的遗传调控。为了研究自我更新和末端不对称分裂的问题，我们选择了几种不同的CNS谱系：MP2、NB7-3、GMC-1->RP2/sib和GMC-1->aCC/pCC谱系。在过去的几年中，我们通过基因筛选发现了一个或多个谱系中表现出自我更新和末端不对称分裂的突变。在这笔赠款中，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自我更新不对称分裂电位中的作用，以及，2) 确定 Neuralized-like 如何抑制前体细胞自我更新不对称分裂电位。细胞，以及 3) 确定 Polycomb（一种染色质重塑蛋白）在 GMC 不对称分裂中的作用。这些研究将有助于了解控制多细胞生物中前体细胞的自我更新和最终不对称分裂的途径。