The UNC-6/netrin guidance cue and its receptors UNC-5 and UNC-40/DCC form a highly conserved system for circumferential guidance of migrating cells and growth cones. In C. elegans, ectopic expression of the UNC-5 receptor causes repulsion of touch neuron growth cones away from sources of UNC-6. A genetic suppressor screen identified 8 genes required for this repulsion:
unc-6,
unc-34,
unc-40,
unc-44,
unc-129,
seu-1,
seu-2, and
seu-3. We have cloned
seu-1 and report that it encodes 2 novel proteins (SEU-1A and SEU-1B), which differ through alternative splicing at their C-termini. Both SEU-1 isoforms contain acidic and proline-rich regions and nuclear localization sequences, but no recognizable DNA- or RNA-binding domains. The
seu-1(
ev520) allele contains an early nonsense mutation and is likely to be a null allele.
seu-1::GFP is nuclear localized and dynamically expressed throughout development in neural and non-neural tissues. Similar to
unc-5 reporter constructs, expression in the hermaphrodite distal tip cells was observed only at the time of the circumferential second migration phase. Transgenic expression of the combination of SEU-1A and SEU-1B in the touch neurons (using the
mec-7 promoter) was sufficient to restore the function of UNC-5 in the touch neurons in a
seu-1 mutant background, suggesting a cell autonomous function. Neither the SEU-1A nor the SEU-1B isoform alone had rescuing ability. Although
seu-1 mutations alone have subtle defects in axonal morphology, over-expression in neurons caused more severe cell migration and axon guidance defects. We propose that SEU-1 in neurons regulates growth cone responses to guidance cues. We are currently examining genetic interactions between
seu-1 and
unc-5,6,40.