RRC ID 57359
Author Amoyel M, Hillion KH, Margolis SR, Bach EA.
Title Somatic stem cell differentiation is regulated by PI3K/Tor signaling in response to local cues.
Journal Development
Abstract Stem cells reside in niches that provide signals to maintain self-renewal, and differentiation is viewed as a passive process that depends on loss of access to these signals. Here, we demonstrate that the differentiation of somatic cyst stem cells (CySCs) in the Drosophila testis is actively promoted by PI3K/Tor signaling, as CySCs lacking PI3K/Tor activity cannot differentiate properly. We find that an insulin peptide produced by somatic cells immediately outside of the stem cell niche acts locally to promote somatic differentiation through Insulin-like receptor (InR) activation. These results indicate that there is a local 'differentiation' niche that upregulates PI3K/Tor signaling in the early daughters of CySCs. Finally, we demonstrate that CySCs secrete the Dilp-binding protein ImpL2, the Drosophila homolog of IGFBP7, into the stem cell niche, which blocks InR activation in CySCs. Thus, we show that somatic cell differentiation is controlled by PI3K/Tor signaling downstream of InR and that the local production of positive and negative InR signals regulates the differentiation niche. These results support a model in which leaving the stem cell niche and initiating differentiation are actively induced by signaling.
Volume 143(21)
Pages 3914-3925
Published 2016-11-1
DOI 10.1242/dev.139782
PII dev.139782
PMID 27633989
PMC PMC5117146
MeSH Animals Animals, Genetically Modified Cell Differentiation* / genetics Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / embryology Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Embryo, Nonmammalian Male Phosphatidylinositol 3-Kinases / metabolism Phosphatidylinositol 3-Kinases / physiology* Proto-Oncogene Proteins c-akt / genetics Signal Transduction / genetics Stem Cell Niche / physiology* Stem Cells / metabolism Stem Cells / physiology* TOR Serine-Threonine Kinases / physiology* Testis / cytology Testis / embryology*
IF 5.413
Drosophila DGRC#103877