C. elegans bicd-1, homolog of the Drosophila dynein accessory factor Bicaudal D, regulates the branching of PVD sensory neuron dendrites
C. elegans bicd-1, homolog of the Drosophila dynein accessory factor Bicaudal D, regulates the branching of PVD sensory neuron dendrites
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DOI：
10.1242/dev.060939
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发表时间：
2011-02-01
期刊：
影响因子：
4.6
通讯作者：
Kaprielian, Zaven
中科院分区：
文献类型：
--
作者：
Aguirre-Chen, Cristina;Buelow, Hannes E.;Kaprielian, Zaven
细胞类型特异性树突分枝模式的建立是神经元电路组装的关键阶段，有助于突触和感觉输入的整合和处理。尽管对果蝇和脊椎动物系统的研究已经确定了调节树突分支形成的多种因素，但控制这一过程的分子机制仍不清楚。在这里，我们介绍了使用秀丽隐杆线虫 PVD 神经元（一对精心设计复杂树突乔木的假定伤害感受器）作为进行高通量 RNAi 筛选的易处理模型，旨在识别树突分支形成的关键调节因子。通过进行两次单独的 RNAi 筛选，一次是基于候选的小规模筛选，另一次是对 IV 号染色体上类似 3000 个基因的大规模筛选，我们检索到了 11 个促进或抑制 PVD 相关树突形成的基因。我们对其中一个基因 bicd-1 进行了详细的功能表征，该基因编码一种微管相关蛋白，此前已证明该蛋白可调节多种生物体中 mRNA 和细胞器的运输。具体来说，我们描述了 bicd-1 在调节树突分支形成中的新作用，并表明 bicd-1 很可能在 PVD 神经元中表达，并且是控制树突分支的主要需要。我们还提供了证据，表明 bicd-1 与 dhc-1 和 unc-116（分别是动力蛋白负端定向和驱动蛋白-1正端定向微管运动复合物的组成部分）在保守途径中运作，并与排斥性引导受体 unc-5 发生遗传相互作用。
The establishment of cell type-specific dendritic arborization patterns is a key phase in the assembly of neuronal circuitry that facilitates the integration and processing of synaptic and sensory input. Although studies in Drosophila and vertebrate systems have identified a variety of factors that regulate dendrite branch formation, the molecular mechanisms that control this process remain poorly defined. Here, we introduce the use of the Caenorhabditis elegans PVD neurons, a pair of putative nociceptors that elaborate complex dendritic arbors, as a tractable model for conducting high-throughput RNAi screens aimed at identifying key regulators of dendritic branch formation. By carrying out two separate RNAi screens, a small-scale candidate-based screen and a large-scale screen of the similar to 3000 genes on chromosome IV, we retrieved 11 genes that either promote or suppress the formation of PVD-associated dendrites. We present a detailed functional characterization of one of the genes, bicd-1, which encodes a microtubule-associated protein previously shown to modulate the transport of mRNAs and organelles in a variety of organisms. Specifically, we describe a novel role for bicd-1 in regulating dendrite branch formation and show that bicd-1 is likely to be expressed, and primarily required, in PVD neurons to control dendritic branching. We also present evidence that bicd-1 operates in a conserved pathway with dhc-1 and unc-116, components of the dynein minus-end-directed and kinesin-1 plus-end-directed microtubule-based motor complexes, respectively, and interacts genetically with the repulsive guidance receptor unc-5.