Regulation of dendrite morphogenseis by Nanos and Pumilio

描述（由申请人提供）：树突树突的组织决定了神经元对细胞外信号的反应效率。尽管已经确定了许多在发育过程中对树突形态的建立至关重要的因素，但对分枝模式随后如何被改进和维持知之甚少。果蝇幼虫的树突树突（da）神经元是鉴定树突形态发生重要基因的基础。Nanos （Nos）和Pumilio （Pum）是果蝇胚胎中翻译抑制复合体的一部分，它们是维持高度分支的IV类da神经元树突树突化所必需的。我们的目标是确定对树突形态发生至关重要的Nos和Pum功能的下游目标。我们实验室最近的遗传分析表明，在nos和泵缺乏的幼虫中观察到的树突树杈缺陷部分是由于促凋亡因子头部退化缺陷（Hid）的表达增加。caspase活性的非凋亡功能，通过凋亡通路成员介导，在许多发育过程中都很重要，包括在变态过程中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验证Nos/Pum复合物通过调节hid调节非凋亡caspase功能，以维持幼虫IV类da神经元在变态前的树突复杂性的假设。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的其他下游靶点。

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.