Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans

Abstract

CERTAIN cell fate decisions are specified by cell–cell interactions during the development of the nematode Caenorhabditis elegans. For example, in a wild-type hermaphrodite gonad, two cells, Z1.ppp and Z4.aaa, have the potential to become the anchor cell (AC)¹. Intercellular communication establishes their fates and ensures that only one cell becomes the AC, while the other becomes a ventral uterine precursor cell (VU)^2,3. One component of this intercellular communication seems to be the 'AC-to-VU' signal from the presumptive AC that causes the other cell to become a VU³. Genetic and developmental studies^3,4 indicate that the lin-12 gene specifies the fates of Z1.ppp and Z4.aaa. Molecular studies^5,6 suggest that lin-12 directly participates in their communications, perhaps acting as the receptor for the 'AC-to-VU' signal³. Here, we report the molecular lesions associated with lin-12 gain-of-function mutations, cell isolation experiments, and genetic studies of an unusual lin-12 allele. These data suggest that self-association of the putative lin-12-encoded receptor leads to its activation, and that certain gain-of-function mutations result in ligand-independent activation.