The
lin-12 gene functions in the decision between alternative cell fates in several sets of cells in C. elegans, including decisions involving cell interactions. The predicted
lin-12 product is a transmembrane protein, and mosaic analysis (Seydoux and Greenwald, Cell 57, p. 1237) has shown that
lin-12 functions in the receiving cell of one of these cell interactions, the anchor cell/ventral uterine (ac/VU) cell interaction. We have identified other genes necesssary for
lin-12 function by screening for extragenic suppressors of the ac/VU cell fate transformation of two
lin-12(d) alleles. We found fourteen mutations in seven genes. Mutations in all seven genes have been tested with at least three different
lin-12(d) alleles for their ability to suppress the ac/VU cell fate transformation, and no allele specificity has been observed. We are now concentrating on two ofthese genes. We have performed mosaic analysis on
sel-5(III). Using sDp3 in
sel-5(
n1254)
ncl-1 unc-36 lin-12(
n302sd) hermaphrodites, we analyzed mosaics for the ac/VU precursor cells. In al sixteen animals found with losses in one of the two cells, the ac was Ncl, suggesting that, like
lin-12,
sel-5 functions in the presumptive VU cells. The two semidominant suppressor alleles of the
sel3(V) gene differ from the other suppressor mutations in that not all
lin-12(d) cell fate transformations are suppressed. For example,
sel-3(
nl255) and
sel-3(
sa37) suppress the ac/VU cell fate transformation, but not the P(3-8).p transformation of
lin-12(d) alleles. Two revertants of
sel-3(
n1255) that no longer suppress
lin12(d) are recessive lethal and fail to complement
let-461 (from D. Baillie) and
lag-2 (from E. Lambie and J. Kimble), and when homozygous, are phenotypically Lag (the
lin-12 and
glp-1 double mutant phenotype). The results suggest that the
sel-3 gene is required for both
lin-12 and
glp-1 functions. In order to clone
sel-3, we are analyzing the dosage of heterozygous deficiency strains on Southern blots, using VL cosmids as probes ( thanks to D. Baillie and R. Horvitz for VL deficiencies.