GLP-1 CAN SUBSTITUTE FOR LIN-12 IN SPECIFYING CELL FATE DECISIONS IN CAENORHABDITIS-ELEGANS

Members of the lin-12/Notch gene family encode receptors for intercell ular signals and are found throughout the animal kingdom. In many anim als, the presence of at least two lin-12/Notch genes raises the issue of the significance of this duplication and divergence. In Caenorhabdi tis elegans, two lin-12/Notch genes, lin-12 and glp-1, encode proteins that are 50% identical, with different numbers of epidermal growth fa ctor-like motifs in their extracellular domains. Many of the cell fate decisions mediated by lin-12 and glp-1 are distinct. Here, we express glp-1 protein under the control of lin-12 regulatory sequences in ani mals lacking endogenous lin-12 activity and find that glp-1 can substi tute for lin-12 in mediating cell fate decisions. These results imply that the lin-12 and glp-1 proteins are biochemically interchangeable, sharing common ligand and effector proteins, and that the discrete lin -12 and glp-1 mutant phenotypes result from differential gene expressi on. In addition, these results suggest that the duplicate lin-12/Notch genes, found in vertebrates may also be biochemically interchangeable .