論文 - 詳細
| RRC ID | 76293 |
|---|---|
| 著者 | Shaul NC, Jordan JM, Falsztyn IB, Ryan Baugh L. |
| タイトル | Insulin/IGF-dependent Wnt signaling promotes formation of germline tumors and other developmental abnormalities following early-life starvation in Caenorhabditis elegans. |
| ジャーナル | Genetics |
| 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. |
| 巻・号 | 223(2) |
| 公開日 | 2023-2-9 |
| DOI | 10.1093/genetics/iyac173 |
| PII | 6855287 |
| PMID | 36449574 |
| PMC | PMC9910406 |
| MeSH | Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Germ Cells / metabolism Insulin / metabolism Neoplasms* Somatomedins* / metabolism Starvation* / genetics Wnt Signaling Pathway |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
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