title: A Caenorhabditis elegans developmental decision requires insulin signaling-mediated neuron-intestine communication.
abstract: Adverse environmental conditions trigger C. elegans larvae to activate an alternative developmental program, termed dauer diapause, which renders them stress resistant. High-level insulin signaling prevents constitutive dauer formation. However, it is not fully understood how animals assess conditions to choose the optimal developmental program. Here, we show that insulin-like peptide (ILP)-mediated neuron-intestine communication plays a role in this developmental decision. Consistent with, and extending, previous findings, we show that the simultaneous removal of INS-4, INS-6 and DAF-28 leads to fully penetrant constitutive dauer formation, whereas the removal of INS-1 and INS-18 significantly inhibits constitutive dauer formation. These ligands are processed by the proprotein convertases PC1/KPC-1 and/or PC2/EGL-3. The agonistic and antagonistic ligands are expressed by, and function in, neurons to prevent or promote dauer formation. By contrast, the insulin receptor DAF-2 and its effector, the FOXO transcription factor DAF-16, function solely in the intestine to regulate the decision to enter diapause. These results suggest that the nervous system normally establishes an agonistic ILP-dominant paradigm to inhibit intestinal DAF-16 activation and allow reproductive development. Under adverse conditions, a switch in the agonistic-antagonistic ILP balance activates intestinal DAF-16, which commits animals to diapause.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, Ontario, M5G 1X5, Canada.
authors.forename: Wesley L
authors.initials: WL
authors.lastname: Hung
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Jyothsna
authors.initials: J
authors.lastname: Chitturi
authors.forename: Mei
authors.initials: M
authors.lastname: Zhen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002450:Cell Communication; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D007814:Larva / Q000378:metabolism; D008954:Models, Biological; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D049452:Green Fluorescent Proteins
keywords: Dauer formation; EGL-3; Insulin; KPC-1