title: LIN-12/Notch regulates lag-1 and lin-12 expression during anchor cell/ventral uterine precursor cell fate specification.
abstract: During Caenorhabditis elegans gonadal development, a stochastic interaction between the LIN-12/Notch receptor and the LAG-2/Delta ligand initiates cell fate specification of two equivalent pre-anchor cell (AC)/pre-ventral uterine (VU) precursor cells. Both cells express lin-12 and lag-2 before specification, and a small difference in LIN-12 activity leads to the exclusive expression of lin-12 in VUs and lag-2 in the AC through an unknown feedback mechanism. In this Notch signaling process, the cleaved LIN-12/Notch intracellular domain (NICD) binds to the LAG-1/CSL transcriptional repressor, forming a transcriptional activator complex containing LAG-1 and NICD. Here we show that clustered LAG-1 binding sites in lin-12 and lag-1 are involved in regulating lin-12 and lag-1 expression during AC/VU cell fate specification. Both genes are expressed in VU cells, but not the AC, after specification. We also show that lin-12 is necessary for lag-1 expression in VU cells. Interestingly, lin-12 (null) animals express lag-1 in the AC, suggesting that LIN-12 signaling is necessary for the suppression of lag-1 expression in the AC. Ectopic expression of lag-1 cDNA in the AC causes a defect in the vulvaluterine (V-U) connection; therefore, LAG-1 should be eliminated in the AC to form a normal V-U connection at a later developmental stage in wild-type animals.
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Seong Kyun
authors.initials: SK
authors.lastname: Park
authors.forename: Vit Na
authors.initials: VN
authors.lastname: Choi
authors.forename: Byung Joon
authors.initials: BJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019521:Body Patterning / Q000235:genetics; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D051880:Receptors, Notch / Q000502:physiology*; D014599:Uterus / Q000166:cytology* / Q000254:growth & development; D014844:Vulva / Q000166:cytology / Q000254:growth & development
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C099355:LAG-1 protein, C elegans; C082460:Lin-12 protein, C elegans; D051880:Receptors, Notch