title: Isoform-specific mutations in the Caenorhabditis elegans heterochronic gene lin-14 affect stage-specific patterning.
abstract: The Caenorhabditis elegans heterochronic gene lin-14 specifies the temporal sequence of postembryonic developmental events. lin-14, which encodes differentially spliced LIN-14A and LIN-14B1/B2 protein isoforms, acts at distinct times during the first larval stage to specify first and second larval stage-specific cell lineages. Proposed models for the molecular basis of these two lin-14 gene activities have included the production of functionally distinct isoforms and the generation of a temporal gradient of LIN-14 protein. We report here that loss of the LIN-14B1/B2 isoforms alone affects one of the two lin-14 temporal patterning functions, the specification of second larval stage lineages. A temporal expression difference between LIN-14A and LIN-14B1/B2 is not responsible for the stage-specific phenotype: protein levels of all LIN-14 isoforms are high in early first larval stage animals and decrease during the first larval stage. However, LIN-14A can partially substitute for LIN-14B1/B2 when expressed at a higher-than-normal level in the late L1 stage. These data indicate that LIN-14B1/B2 isoforms do not provide a distinct function of the lin-14 locus in developmental timing but rather may contribute to an overall level of LIN-14 protein that is the critical determinant of temporal cell fate.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Reinhart
authors.forename: G
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002107:Caenorhabditis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins; D017124:Conserved Sequence; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics*; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C102669:LIN-14 protein, C elegans; D009687:Nuclear Proteins; D020033:Protein Isoforms