In a genetic screen for enhancers of the DTC migration defects of a weak
unc-5 mutation, an allele of the
sdn-1/syndecan gene was isolated. Syndecans are transmembrane proteoglycans with heparan sulfate and possibly chondroitin side chains. As previously reported (Minniti et al., 2004; Rhiner et al., 2005), mutations in
sdn-1 cause defects in egg-laying, neural cell migrations and embryonic development, but do not cause DTC migration defects in an otherwise wild-type genetic background.
sdn-1(
ev697) contains a nonsense mutation predicted to truncate the SDN-1 protein at amino acid 203 in the ectodomain. Our genetic studies suggest that
sdn-1(
ev697) and the null allele
sdn-1(
zh20) disrupt UNC-5-mediated guidance of the DTCs. For example,
unc-5 hypormorphic alleles but not an
unc-5 null are enhanced by
sdn-1 mutations.
By GFP reporter analysis and by immunofluorescence, the
sdn-1 gene is expressed in the hypodermis and nervous system (Minniti et al. 2004; Rhiner et al., 2005). Expression in the DTCs has not been reported. Thus
sdn-1 may act in a cell non-autonomous manner in DTC migrations. Consistent with an indirect mechanism, the enhancement of
unc-5 can be partially suppressed by mutations in growth factor genes, notably
egl-17/FGF and
egl-20/Wnt. These results suggest that EGL-20/Wnt secreted from the tail and EGL-17/FGF secreted from the mid-body influence turning of the DTCs and that SDN-1/syndecan regulates the localization or activity of these growth factors. Consistent with this, we have observed rare, precocious ventral to dorsal migrations of the DTCs in an
egl-20(
mu39) mutant. The frequency of this phenotype is increased in an
egl-20;
egl-17 double mutant. These studies are beginning to yield insight into how anterior-posterior cues interact with dorsoventral cues to produce a patterned cell migration.