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Norway

PMID:38987256  

Regulatory mechanism of cold-inducible diapause in Caenorhabditis elegans.

Makoto Horikawa | Masamitsu Fukuyama | Adam Antebi | Masaki Mizunuma
Nature communications | 2024

Temperature is a critical environmental cue that controls the development and lifespan of many animal species; however, mechanisms underlying low-temperature adaptation are poorly understood. Here, we describe cold-inducible diapause (CID), another type of diapause induced by low temperatures in Caenorhabditis elegans. A premature stop codon in heat shock factor 1 (hsf-1) triggers entry into CID at 9 °C, whereas wild-type animals enter CID at 4 °C. Furthermore, both wild-type and hsf-1(sy441) mutant animals undergoing CID can survive for weeks, and resume growth at 20 °C. Using epistasis analysis, we demonstrate that neural signalling pathways, namely tyraminergic and neuromedin U signalling, regulate entry into CID of the hsf-1 mutant. Overexpression of anti-ageing genes, such as hsf-1, XBP1/xbp-1, FOXO/daf-16, Nrf2/skn-1, and TFEB/hlh-30, also inhibits CID entry of the hsf-1 mutant. Based on these findings, we hypothesise that regulators of the hsf-1 mutant CID may impact longevity, and successfully isolate 16 long-lived mutants among 49 non-CID mutants via genetic screening. Furthermore, we demonstrate that the nonsense mutation of MED23/sur-2 prevents CID entry of the hsf-1(sy441) mutant and extends lifespan. Thus, CID is a powerful model to investigate neural networks involving cold acclimation and to explore new ageing mechanisms.

Pubmed ID: 38987256

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: MEXT | Japan Society for the Promotion of Science (JSPS),
    Id: JP22K06596
  • Agency: Japan Agency for Medical Research and Development (AMED),
    Id: 21gm6110017h0004
  • Agency: Japan Agency for Medical Research and Development (AMED),
    Id: JP22gm6110029
  • Agency: MEXT | Japan Society for the Promotion of Science (JSPS),
    Id: JP22H02260

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This is a list of tools and resources that we have found mentioned in this publication.


Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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RB2600 (organism)

RRID:WB-STRAIN:WBStrain00033275

Caenorhabditis elegans with name hsp-12.1(ok3622) I. from WB.

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RB2612 (organism)

RRID:WB-STRAIN:WBStrain00033286

Caenorhabditis elegans with name hsp-12.2(ok3638) III. from WB.

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OP50 (organism)

RRID:WB-STRAIN:WBStrain00041969

Escherichia coli with name E. coli. from WB.

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N2 (organism)

RRID:WB-STRAIN:WBStrain00000001

Caenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.

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VC475 (organism)

RRID:WB-STRAIN:WBStrain00035801

Caenorhabditis elegans with name hsp-16.2(gk249) V. from WB.

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RB825 (organism)

RRID:WB-STRAIN:WBStrain00031538

Caenorhabditis elegans with name hsp-43(ok647) X. from WB.

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RB791 (organism)

RRID:WB-STRAIN:WBStrain00031504

Caenorhabditis elegans with name hsp-16.48(ok577) V. from WB.

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RB1098 (organism)

RRID:WB-STRAIN:WBStrain00031802

Caenorhabditis elegans with name hsp-12.6(ok1077) IV. from WB.

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