In C. elegans , six vulval precursor cells (VPCs), P3.p through P8.p, are capable of generating vulval cells. In wild-type hermaphrodites, several signaling events (i.e., inducing, lateral, and inhibitory signaling) specify the VPC cell fate pattern 3*-3*-2*-1*-2*-3*. P5.p, P6.p and P7.p adopt vulval fates (1* and 2*), while the other three cells adopt a non-vulval fate (3*). LIN-12 appears to be the receptor for the lateral signal. The lateral signal itself has not been identified in genetic screens, but characterized ligands of LIN-12/Notch receptors all belong to the Delta/Serrate/LAG-2 (DSL) protein family. We have identified a set of DSL genes in the genome --F58B3.8, H02I12.4, W09G12.4, F15B9.3, and F16B12.2, as well as
apx-1 and
arg-1 --to be evaluated as candidates for the lateral signal. The simplest expectation would be that the ligand gene would be expressed in P6.p (and perhaps other VPCs) in the L3 stage after inductive signaling and that loss of ligand activity would lead to the absence of the 2* fate. By both of these criteria,
lag-2 does not appear to be the lateral signal. Some relevant information is available for certain other DSL genes (
apx-1 ,
arg-1 and F15B9.3), but the fact that mutations have not yet identified a candidate ligand may indicate that there is functional redundancy or that loss of gene function has a pleiotropic effect that has precluded its identification in vulval mutant screens. We therefore are screening all candidate DSL genes for their expression in the VPCs, and performing RNAi analysis of various combinations of DSL genes. We will report on our progress at the meeting.