title: DAF-18/PTEN locally antagonizes insulin signalling to couple germline stem cell proliferation to oocyte needs in C. elegans.
abstract: During development, stem cell populations rapidly proliferate to populate the expanding tissues and organs. During this phase, nutrient status, by systemically affecting insulin/IGF-1 signalling, largely dictates stem cell proliferation rates. In adults, however, differentiated stem cell progeny requirements are generally reduced and vary according to the spatiotemporal needs of each tissue. We demonstrate here that differential regulation of germline stem cell proliferation rates in Caenorhabditis elegans adults is accomplished through localized neutralization of insulin/IGF-1 signalling, requiring DAF-18/PTEN, but not DAF-16/FOXO. Indeed, the specific accumulation of oocytes, the terminally differentiated stem cell progeny, triggers a feedback signal that locally antagonizes insulin/IGF-1 signalling outputs in the germ line, regardless of their systemic levels, to block germline stem cell proliferation. Thus, during adulthood, stem cells can differentially respond within tissues to otherwise equal insulin/IGF-1 signalling inputs, according to the needs for production of their immediate terminally differentiated progeny.
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Institut de Recherche en Immunologie et en Cancérologie (IRIC), Université de Montréal, Montréal, Québec, Canada H3T 1J4 patrick.narbonne@umontreal.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Narbonne
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Institut de Recherche en Immunologie et en Cancérologie (IRIC), Université de Montréal, Montréal, Québec, Canada H3T 1J4 Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Maddox
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Institut de Recherche en Immunologie et en Cancérologie (IRIC), Université de Montréal, Montréal, Québec, Canada H3T 1J4.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Labbé
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005854:Germ Cells / Q000166:cytology*; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology*; D015398:Signal Transduction; D013094:Spermatozoa / Q000166:cytology; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C116661:DAF-18 protein, C elegans; D007328:Insulin; D007334:Insulin-Like Growth Factor I
keywords: C. elegans; Feedback regulation; Germline stem cells; Insulin signalling; Oocyte accumulation; Proliferation