C. elegans bicd-1, homolog of theDrosophiladynein accessory factorBicaudal D, regulates the branching of PVD sensory neuron dendrites

Abstract

SUMMARYThe 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-enddirected microtubule-based motor complexes, respectively, and interacts genetically with the repulsive guidance receptor unc-5.

A Dendritic Guidance Receptor Complex Brings Together Distinct Actin Regulators to Drive Efficient F-Actin Assembly and Branching

“…Therefore, it is not surprising that mutations in major actin regulators such as WRC, Rac family of small GTPases (unpublished result, Zou W and Shen K) or TIAM-1 would perturb PVD morphology (Aguirre-Chen et al, 2011; Smith et al, 2010). Nevertheless, it is interesting to compare the loss-of-function phenotypes between the actin regulators and those of dma-1 and hpo-30 .…”

Netrin (UNC-6) mediates dendritic self-avoidance

“…We noted that genetic ablation of the UNC-6 receptors UNC-40/DCC and UNC-5 altered several aspects of PVD morphology (supplemental figure 1 24,26 ) including the aberrant occurrence of overlaps between flanking menorahs in the adult (Fig.2a). We used time-lapse imaging to establish that this mutant phenotype arises from a self-avoidance defect.…”

Skin-Derived Cues Control Arborization of Sensory Dendrites in Caenorhabditis elegans

“…The resulting structures resemble candelabra and have hence been named menorahs (Figures 1A, 1B, and 1D; Oren-Suissa et al, 2010). PVD dendrite formation is perturbed in mutants of the vesicular transport machinery, such as myosin and dynein (Aguirre-Chen et al, 2011), demonstrating that mechanisms of dendrite patterning are conserved in PVD neurons. Other studies have implicated additional genes in the regulation of PVD morphogenesis, such as the fusogen eff-1 (Oren-Suissa et al, 2010) and transcription factors (e.g., unc-86 /BRN3a and mec-3 /Lhx-5; Smith et al, 2010, Smith et al, 2013), and suggested a role for the UNC-6/netrin pathway in PVD dendrite self-avoidance (Smith et al, 2012).…”