daf-2;sea-2

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Genetic mutants with daf-2, sea-2 alterations

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

Temperature °C
20
Lifespan (days)
36.7
Lifespan change (compared to wild type)
112.14%
Phenotype
Loss of function of sea-2 extends the lifespan of daf-2(e1370) mutants.
Lifespan comparisons
Double mutant daf-2(e1370);sea-2(bp283) has a lifespan of 36.7 days, while single mutant daf-2(e1370) has a lifespan of 29.1 days, single mutant sea-2(bp283) has a lifespan of 20.1 days and wild type has a lifespan of 17.3 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Huang X et al., 2011, The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans. Development. 138(10):2059-68 21471153 Click here to select all mutants from this PubMed ID in the graph
Abstract
Like other biological processes, aging is regulated by genetic pathways. However, it remains largely unknown whether aging is determined by an innate programmed timing mechanism and, if so, how this timer is linked to the mechanisms that control developmental timing. Here, we demonstrate that sea-2, which encodes a zinc-finger protein, controls developmental timing in C. elegans larvae by regulating expression of the heterochronic gene lin-28 at the post-transcriptional level. lin-28 is also essential for the autosomal signal element (ASE) function of sea-2 in X:A signal assessment. We also show that sea-2 modulates aging in adulthood. Loss of function of sea-2 slows the aging process and extends the adult lifespan in a DAF-16/FOXO-dependent manner. Mutation of sea-2 promotes nuclear translocation of DAF-16 and subsequent activation of daf-16 targets. We further demonstrate that insulin/IGF-1 signaling functions in the larval heterochronic circuit. Loss of function of the insulin/IGF-1 receptor gene daf-2, which extends lifespan, also greatly enhances the retarded heterochronic defects in sea-2 mutants. Regulation of developmental timing by daf-2 requires daf-16 activity. Our study provides evidence for intricate interplay between the heterochronic circuit that controls developmental timing in larvae and the timing mechanism that modulates aging in adults.

Search genes: daf-2 sea-2

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

173738
sea-2
View on GenAge (sea-2)
WBGene00004751

Signal Element on Autosome

Locus: CELE_K10G6.3

Wormbase description: sea-2 encodes a zinc finger protein; SEA-2 is an autosomal signal element (ASE) that functions to interpret the X:A chromosomal ratio; in addition, SEA-2 functions autonomously in the intestine to regulate adult lifespan and autonomously in seam cells to regulate larval developmental timing; in regulating lifespan and developmental timing, SEA-2 functions as a post-transcriptional negative regulator of LIN-28, which specifies the L2 larval developmental program; sea-2 also interacts with the daf-2/insulin-IGF-1 signaling pathway to regulate larval developmental timing and adult lifespan; a SEA-2::GFP fusion protein is expressed in a variety of tissues, including seam cells, intestinal cells, pharyngeal muscles and nerve ring neurons, and localizes diffusely to the cytoplasm and the nucleus.

Orthologs of daf-2;sea-2 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-2 in SynergyAge

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Species	Gene
Drosophila melanogaster	InR

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

Orthologs of sea-2 in SynergyAge

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Species	Gene