RRC ID 15546
Author Sousa-Nunes R, Yee LL, Gould AP.
Title Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila.
Journal Nature
Abstract Many stem, progenitor and cancer cells undergo periods of mitotic quiescence from which they can be reactivated. The signals triggering entry into and exit from this reversible dormant state are not well understood. In the developing Drosophila central nervous system, multipotent self-renewing progenitors called neuroblasts undergo quiescence in a stereotypical spatiotemporal pattern. Entry into quiescence is regulated by Hox proteins and an internal neuroblast timer. Exit from quiescence (reactivation) is subject to a nutritional checkpoint requiring dietary amino acids. Organ co-cultures also implicate an unidentified signal from an adipose/hepatic-like tissue called the fat body. Here we provide in vivo evidence that Slimfast amino-acid sensing and Target of rapamycin (TOR) signalling activate a fat-body-derived signal (FDS) required for neuroblast reactivation. Downstream of this signal, Insulin-like receptor signalling and the Phosphatidylinositol 3-kinase (PI3K)/TOR network are required in neuroblasts for exit from quiescence. We demonstrate that nutritionally regulated glial cells provide the source of Insulin-like peptides (ILPs) relevant for timely neuroblast reactivation but not for overall larval growth. Conversely, ILPs secreted into the haemolymph by median neurosecretory cells systemically control organismal size but do not reactivate neuroblasts. Drosophila thus contains two segregated ILP pools, one regulating proliferation within the central nervous system and the other controlling tissue growth systemically. Our findings support a model in which amino acids trigger the cell cycle re-entry of neural progenitors via a fat-body-glia-neuroblasts relay. This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour.
Volume 471(7339)
Pages 508-12
Published 2011-3-24
DOI 10.1038/nature09867
PII nature09867
PMID 21346761
PMC PMC3146047
MeSH Adipocytes / drug effects Adipocytes / metabolism* Amino Acids / pharmacology Animals Central Nervous System / cytology Central Nervous System / drug effects Central Nervous System / metabolism Diet Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / drug effects Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism* Fat Body / cytology Fat Body / drug effects Fat Body / metabolism Insulin / metabolism* Larva / cytology Larva / drug effects Larva / metabolism Neural Stem Cells / cytology* Neural Stem Cells / drug effects Neural Stem Cells / metabolism* Neuroglia / drug effects Neuroglia / metabolism* Phosphatidylinositol 3-Kinases / metabolism Signal Transduction / drug effects TOR Serine-Threonine Kinases / metabolism*
IF 42.779
Times Cited 215
Drosophila NP1079-GAL4 (DGRC#103877)