Nematodes can alter their surface composition at the molts between developmental stages. Such surface alterations may enable parasitic nematodes to evade immune attack during the course of infection. We are studying this phenomenon in C. elegans. A specific surface epitope, recognized by monoclonal antibody M37, is normally expressed only at the L1 stage. Two classes of mutants,
srf-6 and temperature sensitive (ts) dauer -constitutive (daf-c), have been identified which bind M37 at later larval stages. This suggests that the
srf-6 and daf-c genes are involved in surface antigen switching. Other than this phenotype,
srf-6 mutants do not share any phenotypes with the ts daf-c mutants. Daf-c mutants grow continuously at 16!C but form dauers at 25!C regardless of environment. Most of the daf-c genes encode components of a TGF-b like signaling pathway. Grenache et al (Proc. Natl. Acad. Sci.USA, Vol 93, pp. 12388-12393, Oct. 1996) showed that
srf-6 appeared to act in surface antigen switching independently of the dauer-defective gene
daf-3, which encodes an SMAD protein that is a downstream component of the TGF-b pathway. This suggests that
srf-6 acts either in parallel with the daf-c genes or downstream of
daf-3 in the TGF-b pathway. To identify possible genetic interactions between
srf-6 and daf-c genes, including the above possibilities, double mutants containing a combination of
srf-6(
yj13) with one of several alleles of each daf-c gene were constructed. We expected that if
srf-6 and a particular daf-c gene acted in parallel pathways, the double mutant might have a more severe phenotype for some aspect of surface antigen switching or dauer formation. Conversely, we expected that if
srf-6 acted in the same pathway, downstream of the daf-c genes, the double and single mutants would have similar phenotypes. Several unexpected results were obtained with a
srf-6(
yj13);
daf-4(
m63) double mutant. Almost 100% of
srf-6(
yj13);
daf-4(
m63) double mutants form dauers at 16!C regardless of environment, while only 4% of the single
daf-4(
m63) form dauers.
daf-4 single mutants are small (the Sma phenotype) but the
srf-6(
yj13);
daf-4(
m63) double mutants are significantly smaller. The
srf-6(
yj13);
daf-4(
m63) adult has an average brood size of 38 (single mutant brood size is 135). Under the same conditions, an increase in dauer formation is also observed in the
srf-6(
yj13);
daf-14(
m77) double mutants (5 % in the single, 55% in the double). Analysis of other
srf-6(
yj13);daf-c double mutants is currently in progress. The increase in dauer formation observed at 16!C in the presence of
srf-6(
yj13) suggests a possible genetic interaction between
srf-6 and daf-c genes. One interpretation of the severe phenotype observed is that
srf-6 and the daf-c genes act in parallel pathways.