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 |