Regulation of dendrite morphogenseis by Nanos and Pumilio

Nanos 和 Pumilio 对树突形态发生的调控

• 批准号: 8717741
• 负责人: Balpreet Bhogal
• 金额: $ 5.7万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8717741
• 关键词: 3' Untranslated Regions; Accounting; Apoptotic; Binding; Biochemical; Biochemical Genetics; Biological Metamorphosis; Caspase; Complex; Cues; Defect; Dendrites; Development; Developmental Process; Down-Regulation; Drosophila genus; Embryo; Etiology; Failure; Gene Expression Regulation; Genes; Genetic; Genetic Suppression; Genetic Translation; Genetic screening method; Head; Larva; Lead; Mediating; Messenger RNA; Molecular; Morphogenesis; Morphology; Nervous System Physiology; Neuronal Dysfunction; Neurons; Pathway interactions; Pattern; Phenotype; Play; Regulation; Response Elements; Role; Signal Transduction; Testing; Training; Translational Repression; extracellular; genetic analysis; insight; member; mutant; nervous system disorder; neuron development; premature; research study

DESCRIPTION (provided by applicant): The organization of dendritic arbors dictates how effectively a neuron can respond to extracellular signals. Although many factors have been identified that are essential for establishing dendritic morphology during development, much less is known about how the branching patterns are subsequently refined and maintained. The well-characterized dendritic arborization (da) neurons in the Drosophila larva have been fundamental in identifying genes that are important for dendrite morphogenesis. Nanos (Nos) and Pumilio (Pum), which were first identified as part of a translational repression complex in the Drosophila embryo, are required to maintain dendritic arborization in the highly branched class IV da neurons. We aim to identify the downstream targets of Nos and Pum function that are essential for dendrite morphogenesis. Recent genetic analyses from our lab suggest that the defects in dendritic arborization observed in nos- and pum-deficient larvae arise partially from an increase in expression of the pro-apoptotic factor Head involution defective (Hid). Nonapoptotic functions of caspase activity, mediated through members of the apoptotic pathway, are important for many developmental processes, including pruning and dendrite remodeling of class IV da neurons during metamorphosis. We propose biochemical and genetic analyses to test the hypothesis that the Nos/Pum complex modulates nonapoptotic caspase function through regulation of hid in order to maintain dendritic complexity in larval class IV da neurons prior to metamorphosis. In addition, a genetic suppression screen will enable us to identify other downstream targets of Nos/Pum that are required for dendrite morphogenesis.

描述（由申请人提供）：树突乔木的组织决定了神经元对细胞外信号做出反应的有效性。尽管已经确定了许多对于发育过程中建立树突形态至关重要的因素，但对于随后如何细化和维持分支模式却知之甚少。果蝇幼虫中已充分表征的树突状树枝化 (da) 神经元对于识别对树突形态发生重要的基因至关重要。 Nanos (Nos) 和 Pumilio (Pum) 最初被鉴定为果蝇胚胎中翻译抑制复合物的一部分，它们是维持高度分支的 IV 类 da 神经元中树突状树枝化所必需的。我们的目标是确定对树突形态发生至关重要的 Nos 和 Pum 功能的下游靶标。我们实验室最近的遗传分析表明，在 nos 和 pum 缺陷的幼虫中观察到的树突分枝缺陷部分是由于促凋亡因子头部退化缺陷 (Hid) 表达的增加所致。通过凋亡途径成员介导的 caspase 活性的非凋亡功能对于许多发育过程都很重要，包括变态过程中 IV 类 da 神经元的修剪和树突重塑。我们提出生化和遗传分析来检验这样的假设：Nos/Pum 复合物通过调节 hid 来调节非凋亡 caspase 功能，以便在变态之前维持幼虫 IV 类 da 神经元的树突复杂性。此外，基因抑制筛选将使我们能够识别树突形态发生所需的 Nos/Pum 的其他下游靶标。