Role of netrin UNC-6 in patterning the longitudinal nerves of Caenorhabditis elegans

The nervous system of Caenorhabditis elegans comprises circumferential and longitudinal axon tracts, Netrin UNC-6 is required for the guidance of circ umferential axon migrations and is expressed by ventral neuroglia and neuro ns in temporally and spatially regulated patterns. Migrating axons mediate the UNC-6 signal through the UNC-5 and UNC-40 receptors, It is thought that UNC-6 is secreted and becomes associated with basement membranes and cell surfaces to form gradients that direct circumferentially migrating axons to ward or away from the ventral UNC-6 sources. Little is known about the effe cts of UNC-6 on longitudinally migrating axons, In unc-6, unc-5, and unc-40 null mutants, some longitudinal nerves are dorsally or ventrally misdirect ed. Furthermore, the organization of axons are disrupted within nerves, We show that cells ectopically expressing UNC-6 can redirect the migrations of some neighboring longitudinal axons, suggesting that the gradients postula ted to direct circumferential migration also help specify the dorsoventral positions of these longitudinal nerves. We also manipulated the temporal an d spatial expression pattern of UNC-6 by two different means, First, me rem oved the PVT midline neuron which expresses UNC-6 for a short time during a xon outgrowths. Second, we expressed UNC-6 uniformly in the nervous system throughout development, The results suggest that changing UNC-6 expression patterns modify the distribution of the cue by providing new localized sour ces. This new guidance information is critical for organizing the axons of longitudinal nerves. (C) 1999 John Wiley & Sons, Inc.