UNC-6 and UNC-40 promote dendritic growth through PAR-4 in Caenorhabditis elegans neurons

Axons navigating through the developing nervous system are instructed by external attractive and repulsive cues. Emerging evidence suggests the same cues control dendrite development, but it is not understood how they differentially instruct axons and dendrites. We studied a C. elegans motor neuron whose axon and dendrite adopt different trajectories and lengths. We found that the guidance cue UNC-6 (Netrin) is required for both axon and dendrite development. Its repulsive receptor UNC-5 repelled the axon from the ventral cell body, whereas the attractive receptor UNC-40 (DCC) was dendritically enriched and promotes antero-posterior dendritic growth. Although the endogenous ventrally secreted UNC-6 instructs axon guidance, dorsal or even membrane-tethered UNC-6 could support dendrite development. Unexpectedly, the serine-threonine kinase PAR-4 (LKB1) was selectively required for the activity of the UNC-40 pathway in dendrite outgrowth. These data suggest that axon and dendrite of one neuron interpret common environmental cues with different receptors and downstream signaling pathways.