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在果蝇神经元形态发生过程中,通过组合使用翻译协同因子进行细胞类型特异性调控。

Combinatorial use of translational co-factors for cell type-specific regulation during neuronal morphogenesis in Drosophila.

机构信息

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

出版信息

Dev Biol. 2012 May 1;365(1):208-18. doi: 10.1016/j.ydbio.2012.02.028. Epub 2012 Feb 25.

Abstract

The translational regulators Nanos (Nos) and Pumilio (Pum) work together to regulate the morphogenesis of dendritic arborization (da) neurons of the Drosophila larval peripheral nervous system. In contrast, Nos and Pum function in opposition to one another in the neuromuscular junction to regulate the morphogenesis and the electrophysiological properties of synaptic boutons. Neither the cellular functions of Nos and Pum nor their regulatory targets in neuronal morphogenesis are known. Here we show that Nos and Pum are required to maintain the dendritic complexity of da neurons during larval growth by promoting the outgrowth of new dendritic branches and the stabilization of existing dendritic branches, in part by regulating the expression of cut and head involution defective. Through an RNA interference screen we uncover a role for the translational co-factor Brain Tumor (Brat) in dendrite morphogenesis of da neurons and demonstrate that Nos, Pum, and Brat interact genetically to regulate dendrite morphogenesis. In the neuromuscular junction, Brat function is most likely specific for Pum in the presynaptic regulation of bouton morphogenesis. Our results reveal how the combinatorial use of co-regulators like Nos, Pum and Brat can diversify their roles in post-transcriptional regulation of gene expression for neuronal morphogenesis.

摘要

转译调控因子 Nanos(Nos)和 Pumilio(Pum)共同调控果蝇幼虫外周神经系统树突分支形态发生。相比之下,Nos 和 Pum 在神经肌肉接头中相互拮抗,调控突触末梢的形态发生和电生理特性。Nos 和 Pum 的细胞功能及其在神经元形态发生中的调节靶标尚不清楚。在这里,我们通过 RNAi 筛选发现翻译共因子脑肿瘤(Brat)在 da 神经元树突形态发生中起作用,并证明 Nos、Pum 和 Brat 在调节树突形态发生方面存在遗传相互作用。在神经肌肉接头中,Brat 功能可能是 Pum 在突触前调节末梢形态发生中的特异性作用。我们的结果揭示了共调节因子如 Nos、Pum 和 Brat 的组合使用如何多样化其在神经元形态发生中转录后基因表达调控中的作用。

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