The C. elegans lag-2 gene is required for several cell-cell interactio
ns that rely on the receptors GLP-1 and LIN-12. Ln this paper, we repo
rt that lag-2 encodes a putative membrane protein with sequence simila
rity to Drosophila Delta, a proposed ligand for the Notch receptor. Fu
rthermore, we show that the lag-2 promoter drives expression of a repo
rter protein in the signaling distal tip cell (DTC) of the DTC/germlin
e interaction. By in situ hybridization, we have found that endogenous
lag-2 mRNA is present in the DTC but not the germ line. One fusion pr
otein, called LAG-2::beta-gal(intra), rescues a lag-2 null mutant and
can be detected in both DTC and germ line. Taking these results togeth
er, we propose that lag-2 may encode a signaling ligand for GLP-1/LIN-
12 and that the entire LAG-2 protein may be taken up into the receivin
g cell during induction by GLP-1 and lateral signaling by LIN-12.