Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Development. 2011 Feb;138(3):507-18. doi: 10.1242/dev.060939.
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 ~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.
神经元回路装配中的一个关键阶段是建立细胞类型特异性树突分支模式,该模式有利于突触和感觉输入的整合和处理。尽管在果蝇和脊椎动物系统中的研究已经确定了多种调节树突分支形成的因素,但控制这一过程的分子机制仍未得到很好的定义。在这里,我们引入秀丽隐杆线虫 PVD 神经元作为一种可行的模型,用于进行高通量 RNAi 筛选,以鉴定控制树突分支形成的关键调节因子。通过进行两次独立的 RNAi 筛选,即小规模基于候选基因的筛选和染色体 IV 上约 3000 个基因的大规模筛选,我们检索到 11 个基因,这些基因要么促进要么抑制与 PVD 相关的树突形成。我们对其中一个基因 bicd-1 进行了详细的功能表征,bicd-1 编码一种微管相关蛋白,先前已显示其在多种生物体中调节 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 可能在 PVD 神经元中表达,并主要需要 bicd-1 来控制树突分支。我们还提供了证据表明 bicd-1 在与 dhc-1 和 unc-116 的保守途径中起作用,dhc-1 和 unc-116 分别是细胞质动力蛋白 minus-end-directed 和驱动蛋白-1 plus-end-directed 微管基运动复合物的组成部分,并且与排斥性导向受体 unc-5 在遗传上相互作用。