LIN-12/Notch proteins function as transmembrane receptors for intercellular signals during development. They are activated by binding of their ligands, DSL (Delta/Serrate/LAG-2) proteins. Ligand binding triggers at least one proteolytic processing event in the extracellular domain and then SEL-12/presenilin-dependent proteolysis within the transmembrane domain. This latter event releases the intracellular domain, which translocates to the nucleus and activates transcription of target genes in a complex with LAG-1, SEL-8, and presumably other proteins. The anchor cell (AC)/ventral uterine precursor cell (VU) fate decision has served as an important model for LIN-12/Notch cell signalling events. Constitutive activation of LIN-12, by
lin-12(d) mutations, causes the presumptive AC to be transformed into a VU. As no AC is made, no vulva is induced, leading to an egg-laying defective (Egl) phenotype. Reversion of the Egl phenotype yields intragenic and extragenic suppressor mutations. Such reversion screens have been carried out on a large scale (Tax et al., 1997; L. Vallier, I. Katic, J. Chen, and I. Greenwald, unpublished observations). Many of the extragenic suppressors, sel genes (suppressor/enhancer of
lin-12), have proven to be critical components of LIN-12/Notch signal transduction. An extragenic suppressor mutation,
n1253, isolated by Tax et al. 1997 defined the
sel-7 gene; our lab has identified an additional allele,
sel-7(
ar516). We have characterized the genetic interaction of these alleles with various alleles of
lin-12 and
glp-1. We have also cloned
sel-7, and found that it encodes a novel protein. We are currently exploring its expression and subcellular localization pattern, and hope to have some insight as to its function in LIN-12/Notch signalling by the meeting.