The elaborate branching patterns displayed by PVD neurons in C. elegans are constrained by the organizing principle of self-avoidance. Self-avoidance is a process in which self-recognition among neurites of a single neuron is followed by their repulsion from each other. This selective repulsion between dendrites of the same cell was originally observed in leech neurons to promote a uniform receptive field. Recent studies by Zipursky and colleagues using Drosophila as a model found that homophilic binding of Dscam1 proteins on sister branches of the same cell (MB or da neurons) promotes repulsive interactions between them, to ensure that they diverge and grow along separate pathways. Since the Dscam1 mutation does not completely disrupt dendrite self-avoidance in Drosophila and there is no Dscam1 homolog in C. elegans, studying PVD dendrite self-avoidance in C. elegans provides a unique opportunity to identify novel mechanisms of dendrite self-avoidance. We isolated mutants through genetic screens that displayed dendrite self-avoidance defects in PVD neurons. We identified mutations in the
kpc-1 gene as being responsible for this defective self-avoidance phenotype through whole genome sequencing.
kpc-1 mutants displayed a significantly lower tertiary branch avoidance index and decreased sensory coverage in the skin compared to wild-type animals. KPC-1 encodes a proprotein convertase subtilisin/kexin (PCSK). Although
kpc-1 has been implicated in dendrite self-avoidance and arborizationa, the mechanism by which
kpc-1 regulates this process is unknown. Here, we show that
kpc-1 functions in PVD neurons to promote dendrite self-avoidance in a
kpc-1 3'UTR dependent manner. We are currently developing an in vivo imaging system to visualize
kpc-1 RNA localization in PVD dendrites and to determine the role of
kpc-1 local translation in dendrite self-avoidance. Reference: a. Dong X, Chiu H, Park YJ, Zou W, Zou Y, Ozkan E, Chang C*, Shen K*. (2016) "Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions," eLife, 5,
e11008. *Co-corresponding authors