Je. Abrahante et al., IDENTIFICATION OF HETEROCHRONIC MUTANTS IN CAENORHABDITIS-ELEGANS - TEMPORAL MISEXPRESSION OF A COLLAGEN /GREEN FLUORESCENT PROTEIN FUSION GENE/, Genetics, 149(3), 1998, pp. 1335-1351
The heterochronic genes lin-4, lin-14, lin-28, and lin-29 specify the
timing of lateral hypodermal seam cell terminal differentiation in Cae
norhabditis elegans. We devised a screen to identify additional genes
involved in this developmental timing mechanism based on identificatio
n of mutants that exhibit temporal misexpression from the col-19 promo
ter, a downstream target of the heterochronic gene pathway. We fused t
he col-19 promoter to the green fluorescent protein gene (gfp) and dem
onstrated that hypodermal expression of the fusion gene is adult-speci
fic in wild-type animals and temporally regulated by the heterochronic
gene pathway. We generated a transgenic strain in which the col-19::g
fp fusion construct is not expressed because of mutation of lin-4 whic
h prevents seam cell terminal differentiation. We have identified and
characterized 26 mutations that restore col-19::gfp expression in the
lin 4 mutant background. Most of the mutations also restore other aspe
cts of the seam cell terminal differentiation program that are defecti
ve in lin-4 mutant animals. Twelve mutations are alleles of three prev
iously identified genes known to be required for proper timing of hypo
dermal terminal differentiation. Among these are four new alleles of l
in-42, a heterochronic gene for which a single allele had been describ
ed previously. Two mutations define a new gene, lin-58. When separated
from lin-4, the lin-58 mutations cause precocious seam cell terminal
differentiation and thus define a new member of the heterochronic gene
pathway.