title: Notch signalling is required for both dauer maintenance and recovery in C. elegans.
abstract: The Notch signalling pathway is conserved among higher metazoans and is used repeatedly throughout development to specify distinct cell fates among populations of equipotent cells. Mounting evidence suggests that Notch signalling may also be crucial in neuronal function in postmitotic, differentiated neurons. Here, we demonstrate a novel role for the canonical Notch signalling pathway in postmitotic neurons during a specialised ;diapause-like' post-embryonic developmental stage in C. elegans called dauer. Our data suggest that cell signalling downstream of the developmental decision to enter dauer leads to the activation of Notch-responding genes in postmitotic neurons. Consistent with this, we demonstrate that glp-1, one of the two C. elegans Notch receptors, and its ligand lag-2 are expressed in neurons during the dauer stage, and both genes are required to maintain this stage in a daf-7/TGFbeta dauer constitutive background. Our genetic data also suggest that a second Notch receptor, lin-12, functions upstream of, or in parallel with, insulin-like signalling components in response to replete growth conditions to promote dauer recovery. Based on our findings, cues associated with the onset of dauer ultimately trigger a glp-1-dependent Notch signalling cascade in neurons to maintain this developmental state. Then, as growth conditions improve, activation of the LIN-12 Notch receptor cooperates with the insulin-like signalling pathway to signal recovery from the dauer stage.
authors.affiliation: Department of Biology, McGill University, Montréal, Québec, Canada.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Ouellet
authors.forename: Shaolin
authors.initials: S
authors.lastname: Li
authors.forename: Richard
authors.initials: R
authors.lastname: Roy
mesh_terms: D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; C099355:LAG-1 protein, C elegans; D008024:Ligands; D008565:Membrane Proteins; D018027:Receptors, Glucagon; D051880:Receptors, Notch; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C086488:lag-2 protein, C elegans; C415502:unc-130 protein, C elegans