daf-2;vang-1

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Genetic mutants with daf-2, vang-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
25
Diet
OP50
Lifespan (days)
25.6
Lifespan change (compared to wild type)
150.98%
Phenotype
Depletion of DAF-2 by RNAi in tm1422 and WT causes an increase of mean life span to 25.6 and 25.8 which is in agreement with published results for daf-2 mutants. RNAi against daf-2 in WT and tm1422 worms resulted in nearly identical survival curves with no significant difference in mean life span, indicating that vang-1 may function in the insulin/IGF-1-like signaling pathway, rather than in parallel pathways, e.g., through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling.
Lifespan comparisons
Double mutant daf-2(RNAi);vang-1(tm1422) has a lifespan of 25.6 days, while single mutant daf-2(RNAi) has a lifespan of 25.8 days, single mutant vang-1(tm1422) has a lifespan of 14.3 days and wild type has a lifespan of 10.2 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Honnen SJ et al., 2012;7(2):e32183., C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling. PLoS One. 7(2):e32183 22359667 Click here to select all mutants from this PubMed ID in the graph
Abstract
The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans.

Search genes: daf-2 vang-1

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Entrez ID
Symbol
GenAge
Wormbase ID

180579
vang-1
View on GenAge (vang-1)
WBGene00015171

Vang-like protein

Locus: CELE_B0410.2

Wormbase description: vang-1 encodes an ortholog of Drosophila STRABISMUS/VAN GOGH; vang-1 enables Wnt-directed planar cell polarity; VANG-1 is required for the fully asymmetrical division of B.a versus B.p cells, though this requirement is quantitatively weak; vang-1 also negatively regulates adult lifespan via the DAF-2/IGFR insulin signaling pathway, and also plays a role in thermal tolerance and response to oxidative stress.

Orthologs of daf-2;vang-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	InR;Vang
Mus musculus	Insr;Vangl1
Mus musculus	Insr;Vangl2
Mus musculus	Igf1r;Vangl1
Mus musculus	Igf1r;Vangl2
Mus musculus	Insrr;Vangl1
Mus musculus	Insrr;Vangl2

Orthologs of daf-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr

Orthologs of vang-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Vang
Mus musculus	Vangl1
Mus musculus	Vangl2