biostudies-literatureUnknown21(12)Falsztyn IBEarly life experiences such as malnutrition can affect development and adult disease risk, but the molecular basis of such protracted effects is poorly understood. In the nematode C. elegans, extended starvation during the first larval stage causes the development of germline tumors and other abnormalities in the adult gonad, limiting reproductive success. Insulin/IGF signaling (IIS) acts through WNT signaling and lipid metabolism to promote starvation-induced gonad abnormalities, but IIS-independent modifiers have not been identified. The tumor suppressor daf-18/PTEN inhibits IIS to suppress starvation-induced abnormalities, but we show that it also acts independently of IIS via lin-35/Rb, another tumor suppressor, to suppress such abnormalities. We found that lin-35/Rb and the rest of thPLoS geneticse1011641https://www.ebi.ac.uk/biostudies/studies/S-EPMC12674584biostudies-literatureEarly life starvation and Hedgehog-related signaling activate innate immunity downstream of daf-18/PTEN and lin-35/Rb causing developmental pathology in adult C. elegans.PMC12674584Falsztyn IBJordan JMReinke AWBaugh LRChen JChitrakar RZhao WfalseEarly life starvation and Hedgehog-related signaling activate innate immunity downstream of daf-18/PTEN and lin-35/Rb causing developmental pathology in adult C. elegans.Early life experiences such as malnutrition can affect development and adult disease risk, but the molecular basis of such protracted effects is poorly understood. In the nematode C. elegans, extended starvation during the first larval stage causes the development of germline tumors and other abnormalities in the adult gonad, limiting reproductive success. Insulin/IGF signaling (IIS) acts through WNT signaling and lipid metabolism to promote starvation-induced gonad abnormalities, but IIS-independent modifiers have not been identified. The tumor suppressor daf-18/PTEN inhibits IIS to suppress starvation-induced abnormalities, but we show that it also acts independently of IIS via lin-35/Rb, another tumor suppressor, to suppress such abnormalities. We found that lin-35/Rb and the rest of th2025-01-01T00:00:00Z2025 Dec2026-05-22T03:22:16.831Z2026-05-22T03:15:04.897ZS-EPMC126745844133684510.1371/journal.pgen.1011641