Heterochronic genes regulate developmental timing in C. elegans . In a recent publication, we described our analysis of the
lin-66 gene that was identified by isolating two suppressor mutations 1. We showed that
lin-66 mutations cause retarded heterochronic phenotypes in seam cell and vulval cell lineages and die at the late L4 stage. Further analysis also indicates that
lin-66 regulates the L2 to L3 transition of seam cell development by regulating the expression of
lin-28. Our results also suggest that
lin-66 regulation of
lin-28 expression is parallel to three other mechanisms that regulate
lin-28 expression, including LIN-14-mediated up-regulation, miRNA-mediated repression, and DAF-12-involved translational promotion. Although our data suggest that the regulation is mediated by the 3 UTR of
lin-28, the mechanism of this regulation is currently not understood. Our further biochemical analysis of
lin-66 interacting proteins has not been fruitful. To obtain more insight into the molecular mechanism of
lin-66 function, we carried out screens for suppressors of the
lin-66(lf) mutation. Because
lin-31(lf) can suppress the lethality of
lin-66(lf), we used the
lin-31;
lin-66 double mutant as the starting strain. We screened more than 30, 000 haploid genomes and isolated 7 mutations that suppress the retarded heterochronic phenotype in hypodermal alae formation of
lin-66(lf). We are currently mapping the suppressors. We will present the SNP mapping data at the meeting. (1). Morita K and Han M, (2006) Multiple mechanisms are involved in regulating the expression of the developmental timing regulator
lin-28 in C. elegans. EMBO J, 25 5794-5804.