Organ-specific cell division abnormalities caused by mutation in a general cell cycle regulator in C. elegans.
The precise control of cell division during development is pivotal for morphogenesis and the correct formation of tissues and organs. One important gene family involved in such control is the p21/p27/p57 class of negative cell cycle regulators. Loss of function of the C. elegans p27 homolog, cki-1, causes extra cell divisions in numerous tissues including the hypodermis, the vulva, and the intestine. We have sought to better understand how cell divisions are controlled upstream or in parallel to cki-1 in specific organs during C. elegans development. By taking advantage of the invariant cell lineage of C. elegans, we used an intestinal-specific GFP reporter in a screen to identify mutants that undergo cell division abnormalities in the intestinal lineage. We have isolated a mutant with twice the wild-type complement of intestinal cells, all of which arise during mid-embryogenesis. This mutant, called rr31, is a fully dominant, maternal-effect, gain-of-function mutation in the cdc-25.1 cell cycle phosphatase that sensitizes the intestinal lineage to an extra cell division. We showed that cdc-25.1 acts at the G1/S transition, as ectopic expression of CDC-25.1 caused entry into S phase in intestinal cells. In addition, we showed that the cdc-25.1(gf) requires cyclin E. The extra cell division defect was shown to be restricted to the E lineage and the E fate is necessary and sufficient to sensitize cells to this mutation.
Kostić
Ivana
I
Department of Biology, McGill University, Montreal, Quebec, Canada.
Roy
Richard
R
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002452:Cell Count; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018509:DNA, Helminth / Q000235:genetics; D005260:Female; D017238:Genes, Helminth; D007422:Intestines / Q000166:cytology / Q000196:embryology; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D009928:Organ Specificity; D010641:Phenotype; D020687:cdc25 Phosphatases / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018509:DNA, Helminth; C115024:cki-1 protein, C elegans; D020687:cdc25 Phosphatases