title: Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila.
abstract: The interconnected Insulin/IGF signaling (IlS) and Target of Rapamycin (TOR) signaling pathways constitute the main branches of the nutrient-sensing system that couples growth to nutritional conditions in Drosophila. Here, we addressed the influence of these pathways and of diet restriction on the balance between the maintenance of multipotent hematopoietic progenitors and their differentiation in the Drosophila lymph gland. In this larval hematopoietic organ, a pool of stem-like progenitor blood cells (prohemocytes) is kept undifferentiated in response to signaling from a specialized group of cells forming the posterior signaling center (PSC), which serves as a stem cell niche. We show that, reminiscent of the situation in human, loss of the negative regulator of IIS Pten results in lymph gland hyperplasia, aberrant blood cell differentiation and hematopoietic progenitor exhaustion. Using site-directed loss- and gain-of-function analysis, we demonstrate that components of the IIS/TOR pathways control lymph gland homeostasis at two levels. First, they cell-autonomously regulate the size and activity of the hematopoietic niche. Second, they are required within the prohemocytes to control their growth and maintenance. Moreover, we show that diet restriction or genetic alteration mimicking amino acid deprivation triggers progenitor cell differentiation. Hence, our study highlights the role of the IIS/TOR pathways in orchestrating hematopoietic progenitor fate and links blood cell fate to nutritional status.
authors.affiliation: Université de Toulouse, UPS, CBD (Centre de Biologie du Développement), Bâtiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France.
authors.forename: Billel
authors.initials: B
authors.lastname: Benmimoun
authors.forename: Cédric
authors.initials: C
authors.lastname: Polesello
authors.forename: Lucas
authors.initials: L
authors.lastname: Waltzer
authors.forename: Marc
authors.initials: M
authors.lastname: Haenlin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D008208:Lymphatic System / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D058570:TOR Serine-Threonine Kinases