RRC ID 59515
著者 Jordan JM, Hibshman JD, Webster AK, Kaplan REW, Leinroth A, Guzman R, Maxwell CS, Chitrakar R, Bowman EA, Fry AL, Hubbard EJA, Baugh LR.
タイトル Insulin/IGF Signaling and Vitellogenin Provisioning Mediate Intergenerational Adaptation to Nutrient Stress.
ジャーナル Curr Biol
Abstract The roundworm C. elegans reversibly arrests larval development during starvation [1], but extended early-life starvation reduces reproductive success [2, 3]. Maternal dietary restriction (DR) buffers progeny from starvation as young larvae, preserving reproductive success [4]. However, the developmental basis of reduced fertility following early-life starvation is unknown, and it is unclear how maternal diet modifies developmental physiology in progeny. We show here that extended starvation in first-stage (L1) larvae followed by unrestricted feeding results in a variety of developmental abnormalities in the reproductive system, including proliferative germ-cell tumors and uterine masses that express neuronal and epidermal cell fate markers. We found that maternal DR and reduced maternal insulin/insulin-like growth factor (IGF) signaling (IIS) increase oocyte provisioning of vitellogenin lipoprotein, reducing penetrance of starvation-induced abnormalities in progeny, including tumors. Furthermore, we show that maternal DR and reduced maternal IIS reduce IIS in progeny. daf-16/FoxO and skn-1/Nrf, transcriptional effectors of IIS, are required in progeny for maternal DR and increased vitellogenin provisioning to suppress starvation-induced abnormalities. daf-16/FoxO activity in somatic tissues is sufficient to suppress starvation-induced abnormalities, suggesting cell-nonautonomous regulation of reproductive system development. This work reveals that early-life starvation compromises reproductive development and that vitellogenin-mediated intergenerational insulin/IGF-to-insulin/IGF signaling mediates adaptation to nutrient availability.
巻・号 29(14)
ページ 2380-2388.e5
公開日 2019-7-22
DOI 10.1016/j.cub.2019.05.062
PII S0960-9822(19)30676-1
PMID 31280992
PMC PMC6650306
MeSH Adaptation, Physiological* Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Insulin / metabolism Larva / genetics Larva / growth & development Larva / physiology Nutrients / physiology Signal Transduction* Somatomedins / metabolism Vitellogenins / metabolism
IF 9.193
引用数 7
リソース情報
線虫 tm4063 tm1200