UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites

Axon guidance: cue here Neurons are highly polarized cells with distinct functional compartments — the dendrites and axons — that gate information input and output, respectively. Strict segregation of specific proteins to one or the other compartment, a phenomenon called cell polarization, is thought to be controlled intrinsically. New work by Vivian Poon et al . shows that in nematodes, the extracellular molecule Unc6/Netrin is both required in the vicinity of dendrites to prevent mislocalization of axonal proteins there, and is sufficient to exclude synaptic proteins from axon terminals if artificially provided close to these. The results extend to another extracellular protein, Wnt, and suggest that axon guidance cues also control local exclusion of axon terminal components from dendrites. In nematodes, the extracellular molecule UNC6/netrin is required both in the vicinity of dendrites to prevent mislocalization of axonal proteins there, and sufficient to exclude synaptic proteins from axon terminals if artificially provided close to these. The results extend to another extracellular protein, Wnt, and suggest that axon guidance cues also control local exclusion of axon terminal components from dendrites. Polarity is an essential feature of many cell types, including neurons that receive information from local inputs within their dendrites and propagate nerve impulses to distant targets through a single axon. It is generally believed that intrinsic structural differences between axons and dendrites dictate the polarized localization of axonal and dendritic proteins 1 . However, whether extracellular cues also instruct this process in vivo has not been explored. Here we show that the axon guidance cue UNC-6/netrin and its receptor UNC-5 act throughout development to exclude synaptic vesicle and active zone proteins from the dendrite of the Caenorhabditis elegans motor neuron DA9, which is proximal to a source of UNC-6/netrin. In unc-6/netrin and unc-5 loss-of-function mutants, presynaptic components mislocalize to the DA9 dendrite. In addition, ectopically expressed UNC-6/netrin, acting through UNC-5, is sufficient to exclude endogenous synapses from adjacent subcellular domains within the DA9 axon. Furthermore, this anti-synaptogenic activity is interchangeable with that of LIN-44/Wnt despite being transduced through different receptors, suggesting that extracellular cues such as netrin and Wnts not only guide axon navigation but also regulate the polar