We have been studying the role of the
sel-1 gene, an apparent negative regulator of
lin-12 and
glp-1 activity. In order to better understand the role of
sel-1 in
lin-12 mediated signaling, we have determined the null phenotype, gene specificity, molecular nature, and expression pattern of the
sel-1 gene. The
sel-1 null phenotype is wild-type in a
lin-12(+) background. However the phenotypic consequences of loss of
sel-1 function in a sensitized genetic background (e.g.
lin-12(
n676n930ts)) are dramatic, revealing an increase in apparent
lin-12 activity. This may indicate that
sel-1 fine tunes
lin-12 activity within a limited range. Alternatively,
sel-1 may be genetically redundant with other genes providing an essential function in
lin-12 - mediated signaling. We note however that genes with small effects on
lin-12 activity may be very important for
lin-12-mediated decision-making, since small differences in
lin-12 activity between interacting cells are greatly amplified by feedback regulation, leading to changes in cell fate. Previous work had shown
sel-1 to be a gene specific suppressor. In order to test futher the hypothesis that suppression by
sel-1 is
lin-12/glp-1 specific, we tested the ability of
sel-1 to suppress mutations in other receptors and/or ligands. We found that
sel-1 fails to suppress mutations in
let-23,
lin-3,
egl-15,
daf-4, and
tra-2. We have cloned and sequenced the
sel-1 locus, and have found that
sel-1 encodes a predicted extracellular protein which may be anchored to the cell surface. In addition to confirming the
sel-1(0) phenotype, sequence analysis of
sel-1 mutants has shown that several mutant lesions alter the predicted amino acid sequence in a region of high similarity between SEL-1 and yeast hypothetical protein L8167.5. Recently we have begun studying the expression pattern of
sel-1::lacZ and
sel-1::gfp reporter constructs. We have observed expression in the intestine, neurons of the head ganglia, excretory cell, and unidentified cells in the tail. However we have not observed expression in the somatic gonad or VPCs, two places where
lin-12 is expressed and required. This result suggests the interesting possibility that
sel-1 is produced at a distant site and diffuses to interact with cells undergoing cell fate decisions. We are now attempting to confirm this expression pattern by independent methods, and testing the ability of
sel-1 to affect cell fates when produced by a distant source.