Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Aug 15;22(16):2149-65.
doi: 10.1101/gad.1701508.

C. elegans dauer formation and the molecular basis of plasticity

Nicole Fielenbach  1 , Adam Antebi
Affiliations
Review

C. elegans dauer formation and the molecular basis of plasticity

Nicole Fielenbach et al. Genes Dev. .

Abstract

Because life is often unpredictable, dynamic, and complex, all animals have evolved remarkable abilities to cope with changes in their external environment and internal physiology. This regulatory plasticity leads to shifts in behavior and metabolism, as well as to changes in development, growth, and reproduction, which is thought to improve the chances of survival and reproductive success. In favorable environments, the nematode Caenorhabditis elegans develops rapidly to reproductive maturity, but in adverse environments, animals arrest at the dauer diapause, a long-lived stress resistant stage. A molecular and genetic analysis of dauer formation has revealed key insights into how sensory and dietary cues are coupled to conserved endocrine pathways, including insulin/IGF, TGF-beta, serotonergic, and steroid hormone signal transduction, which govern the choice between reproduction and survival. These and other pathways reveal a molecular basis for metazoan plasticity in response to extrinsic and intrinsic signals.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
(A) C. elegans life cycle. In favorable environments, C. elegans undergoes reproductive development and progresses rapidly from embryo through four larval stages (L1–L4) to the adult in 3–5 d (15°C–20°C). Adults then live another 2–3 wk. In unfavorable conditions, including overcrowding, limited food, and high temperature, C. elegans undergoes development to a specialized third larval stage called the dauer diapause (L3d), which can live several months. Upon return to favorable environments, dauer larvae recover to reproductive adults with normal life spans. (B) Schematic of neuroendocrine cells. Integration of environmental cues (dauer pheromone, nutrients, and temperature) are transformed into endocrine signals by amphid neurons (ASI, ADF, ASG, ASJ, ASK, AWA, and AWC). Serotonergic signaling from ADF and cGMP signaling from ASJ and ASK influence production of TGF-β from ASI and the ILPs from ASI, ASJ, and other cells. Insulin/IGF-1 signaling and TGF-β signaling converge on steroid hormone signaling in the XXX cells. Not shown are the other tissues where ILP and steroid hormone production take place. SKN-1 also works in the ASI neuron to regulate DR-induced longevity.
Figure 2.
Figure 2.
A model for the regulatory plasticity of dauer formation. Environmental cues (dauer pheromone and nutrients) are detected by GPCRs that reside in the ciliary endings of amphid neurons. These signals may be transduced via G-proteins together with the transmembrane GCY DAF-11, which converts GTP to cGMP. cGMP gated ion channels, TAX-2/TAX-4, transduce cGMP levels into ion influx. (Left) For reproductive development, high cGMP levels, directly or indirectly, lead to production of TGF-β (in ASI) and ILPs in amphids and other tissues. In endocrine cells (e.g., XXX, hypodermal, intestinal cells), binding of ILP agonists to the insulin/IGF-1 receptor DAF-2 results in activation of the AGE-1/PI3Kinase and PIP3 production. Presence of PI3 lipids and activating kinase PDK-1, leads to activation of AKT1,2 and SGK kinases, which phosphorylate DAF-16/FOXO, resulting in cytoplasmic retention by FTT-2/14-3-3 proteins. Binding of DAF-7/TGF-β to the DAF-1/4 receptor kinases results in phosphorylation of DAF-8 and DAF-14/ SMADs, and inhibition of DAF-3/SMAD and DAF-5/SNO-SKI complexes. Nuclear localization of DAF-8 and DAF-14 SMADs directly or indirectly regulates expression of hormone synthesis enzymes (e.g., DAF-9/CYP450), which produce dafachronic acids, the ligands for DAF-12/NHR. Niemann-Pick homologs NCR-1,2 deliver cholesterol and other sterols for use in hormone biosynthesis. In target tissues, liganded DAF-12 promotes reproductive and inhibits dauer programs. (Right) In dauer inducing conditions, low levels of cGMP diminish ILPs and TGF-β production. Down-regulated ILP and TGF-β production results in nuclear translocation of DAF-16/FOXO and DAF-3/DAF-5/SMADs to promote dauer programs and directly or indirectly inhibit expression of hormone biosynthetic genes. In target tissues, unliganded DAF-12 promotes dauer programs and through association with its corepressor DIN-1/SHARP represses reproductive programs. Note that the identified signaling pathways do not necessarily work in a strictly hierarchical fashion, can work in parallel, and have independent outputs.
Figure 3.
Figure 3.
Heterochronic loci and control of developmental timing. The heterochronic pathway controls temporal development specifying stage appropriate programs for each larval stage. Upon hatching, food signals lead to up-regulation of lin-4/miRNA, which down-regulates its targets LIN-14/NUCLEAR PROTEIN and LIN-28/RNA BINDING PROTEIN, resulting in L1-to-L2 transitions. Up-regulation of let-7 microRNA family members (mir-48, mir-84, and mir-241) down-regulate hbl-1/HUNCHBACK to trigger the L2/L3 transitions. DAF-12/NHR integrates environmental signals from the dauer pathways (cGMP, serotonin, insulin, and TGF-β). In unfavorable environmental conditions, unliganded DAF-12 together with its corepressor DIN-1/SHARP shut down the heterochronic circuit and specify dauer development. In favorable environmental conditions, liganded DAF-12 advances the heterochronic circuit to the L3 stage, and thus promotes reproductive development and maturation (for details, see Fig. 2 and the text). Several gene products control late larval development by preventing expression of LIN-29/ZnF transcription factor, which is instructive for adult development. The larval-to-adult transition is triggered through expression of let-7/miRNA, which leads to down-regulation of LIN-41/RBCC protein and up-regulation of LIN-29/ZnF transcription factor. Not all heterochronic activites are shown.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abbott A.L., Alvarez-Saavedra E., Miska E.A., Lau N.C., Bartel D.P., Horvitz H.R., Ambros V. The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev. Cell. 2005;9:403–414. - PMC - PubMed
    1. Abrahante J.E., Daul A.L., Li M., Volk M.L., Tennessen J.M., Miller E.A., Rougvie A.E. The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Dev. Cell. 2003;4:625–637. - PubMed
    1. Ailion M., Thomas J.H. Dauer formation induced by high temperatures in C. elegans. Genetics. 2000;156:1047–1067. - PMC - PubMed
    1. Ailion M., Thomas J.H. Isolation and characterization of high-temperature-induced dauer formation mutants in Caenorhabditis elegans. Genetics. 2003;165:127–144. - PMC - PubMed
    1. Ailion M., Inoue T., Weaver C.I., Holdcraft R.W., Thomas J.H. Neurosecretory control of aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. 1999;96:7394–7397. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources