An insulin receptor activity surge in follicle cells drives vitellogenesis by upregulating CrebA
Xiaoya Wang, Huanju Liu, Zhiyong Yin, Tianning Shao, Lin Li, Jun Ma, Feng He
TL;DR
Insulin signaling in fruit fly follicle cells boosts yolk production through a protein called CrebA, and this mechanism is conserved in human cells.
Contribution
The study identifies a conserved regulatory axis involving insulin signaling, CrebA, and FoxO in follicle cells across species.
Findings
Insulin receptor activity surges in Drosophila follicle cells during vitellogenesis.
CrebA activates genes for yolk and membrane proteins, and its expression is suppressed by FoxO under insulin disruption or high-sucrose diets.
The FOXO1-CREB3L2 module in human granulosa cells mirrors the Drosophila regulatory mechanism.
Abstract
Folliculogenesis is a process that requires accurate interpretation of female physiological cues and elaborate coordination between the growing oocyte and its surrounding follicle cells, each being capable of responding to external signals. Here, we investigate the role of insulin signaling in Drosophila follicle cells. Using a phase separation-based reporter system, we observe a surge of insulin receptor activity in follicle cells during vitellogenic stages, a surge that is disrupted by a maternal high-sucrose diet. Single-cell RNA-seq reveals a diet-sensitive subpopulation of stage-8 follicle cells, which exhibits a reduction in CrebA-mediated transcription of genes for yolk and vitelline membrane proteins. Our results suggest a critical role of CrebA in implementing the stage-specific effect of insulin signaling to boost the secretory capacity of follicle cells. Mechanistically,…
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Taxonomy
TopicsDevelopmental Biology and Gene Regulation · Hippo pathway signaling and YAP/TAZ · Reproductive Biology and Fertility