Nutrition-Responsive Glia Control Exit of Neural Stem Cells from Quiescence

Summary

The systemic regulation of stem cells ensures that they meet the needs of the organism during growth and in response to injury. A key point of regulation is the decision between quiescence and proliferation. During development, Drosophila neural stem cells (neuroblasts) transit through a period of quiescence separating distinct embryonic and postembryonic phases of proliferation. It is known that neuroblasts exit quiescence via a hitherto unknown pathway in response to a nutrition-dependent signal from the fat body. We have identified a population of glial cells that produce insulin/IGF-like peptides in response to nutrition, and we show that the insulin/IGF receptor pathway is necessary for neuroblasts to exit quiescence. The forced expression of insulin/IGF-like peptides in glia, or activation of PI3K/Akt signaling in neuroblasts, can drive neuroblast growth and proliferation in the absence of dietary protein and thus uncouple neuroblasts from systemic control.

Abstract

Graphical Abstract

Highlights

► Stellate glia express insulin/IGF-like peptides (dILPs) in response to nutrition ► Insulin receptor/PI3K signaling is required for neural stem cell (NSC) reactivation ► Glial dILP expression is sufficient to reactivate NSCs irrespective of nutrition ► Glial signaling is essential for NSC exit from quiescence