title: Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance.
abstract: Adipocytes have key endocrine roles, mediated in large part by secreted protein hormones termed adipokines. The adipokine adiponectin is well known for its role in sensitizing peripheral tissues to insulin, and several lines of evidence suggest that adiponectin might also modulate stem cells/precursors. It remains unclear, however, how adiponectin signaling controls stem cells and whether this role is secondary to its insulin-sensitizing effects or distinct. Drosophila adipocytes also function as an endocrine organ and, although no obvious adiponectin homolog has been identified, Drosophila AdipoR encodes a well-conserved homolog of mammalian adiponectin receptors. Here, we generate a null AdipoR allele and use clonal analysis to demonstrate an intrinsic requirement for AdipoR in germline stem cell (GSC) maintenance in the Drosophila ovary. AdipoR null GSCs are not fully responsive to bone morphogenetic protein ligands from the niche and have a slight reduction in E-cadherin levels at the GSC-niche junction. Conversely, germline-specific overexpression of AdipoR inhibits natural GSC loss, suggesting that reduction in adiponectin signaling might contribute to the normal decline in GSC numbers observed over time in wild-type females. Surprisingly, AdipoR is not required for insulin sensitization of the germline, leading us to speculate that insulin sensitization is a more recently acquired function than stem cell regulation in the evolutionary history of adiponectin signaling. Our findings establish Drosophila female GSCs as a new system for future studies addressing the molecular mechanisms whereby adiponectin receptor signaling modulates stem cell fate.
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Baltimore, MD, USA.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Laws
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Baltimore, MD, USA.
authors.forename: Leesa L
authors.initials: LL
authors.lastname: Sampson
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Baltimore, MD, USA; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. Electronic address: dbarbosa@jhu.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Drummond-Barbosa
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005854:Germ Cells / Q000166:cytology*; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D007328:Insulin; D054419:Receptors, Adiponectin; C586408:adiponectin receptor, Drosophila
keywords: AdipoR; Adiponectin; Diet; Drosophila; Germline stem cell; Oogenesis