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- W4310433630 abstract "The Developmental Origins of Health and Disease hypothesis postulates that early-life stressors can predispose people to disease later in life. In the roundworm Caenorhabditis elegans, prolonged early-life starvation causes germline tumors, uterine masses, and other gonad abnormalities to develop in well-fed adults. Reduction of insulin/insulin-like growth factor (IGF) signaling (IIS) during larval development suppresses these starvation-induced abnormalities. However, molecular mechanisms at play in formation and suppression of starvation-induced abnormalities are unclear. Here we describe mechanisms through which early-life starvation and reduced IIS affect starvation-induced abnormalities. Transcriptome sequencing revealed that expression of genes in the Wnt signaling pathway is upregulated in adults starved as young larvae, and that knockdown of the insulin/IGF receptor daf-2/InsR decreases their expression. Reduction of Wnt signaling through RNAi or mutation reduced starvation-induced abnormalities, and hyperactivation of Wnt signaling produced gonad abnormalities in worms that had not been starved. Genetic and reporter-gene analyses suggest that Wnt signaling acts downstream of IIS in the soma to cell-nonautonomously promote germline hyperproliferation. In summary, this work reveals that IIS-dependent transcriptional regulation of Wnt signaling promotes starvation-induced gonad abnormalities, illuminating signaling mechanisms that contribute to adult pathology following early-life starvation." @default.
- W4310433630 created "2022-12-10" @default.
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- W4310433630 date "2022-11-30" @default.
- W4310433630 modified "2023-09-24" @default.
- W4310433630 title "Insulin/IGF-dependent Wnt signaling promotes formation of germline tumors and other developmental abnormalities following early-life starvation in <i>Caenorhabditis elegans</i>" @default.
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- W4310433630 doi "https://doi.org/10.1093/genetics/iyac173" @default.
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