title: Apontic regulates somatic stem cell numbers in Drosophila testes.
abstract: BACKGROUND
  Microenvironments called niches maintain resident stem cell populations by balancing self-renewal with differentiation, but the genetic regulation of this process is unclear. The niche of the Drosophila testis is well-characterized and genetically tractable, making it ideal for investigating the molecular regulation of stem cell biology. The JAK/STAT pathway, activated by signals from a niche component called the hub, maintains both germline and somatic stem cells.
  
  
  RESULTS
  This study investigated the molecular regulation of the JAK/STAT pathway in the stem cells of the Drosophila testis. We determined that the transcriptional regulator Apontic (Apt) acts in the somatic (cyst) stem cells (CySCs) to balance differentiation and maintenance. We found Apt functions as a negative feedback inhibitor of STAT activity, which enables cyst cell maturation. Simultaneous loss of the STAT regulators apt and Socs36E, or the Stat92E-targeting microRNA miR-279, expanded the somatic stem cell-like population.
  
  
  CONCLUSIONS
  Genetic analysis revealed that a conserved genetic regulatory network limits JAK/STAT activity in the somatic stem cells of Drosophila testis. In these cells, we determined JAK/STAT signaling promotes apt expression. Then, Apt functions through Socs36E and miR-279 to attenuate pathway activation, which is required for timely CySC differentiation. We propose that Apt acts as a core component of a STAT-regulatory circuit to prevent stem cell overpopulation and allow stem cell maturation.
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD, 21250, USA.|Present Address: Department of Medicine, Division of Infectious Disease, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Monahan
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD, 21250, USA. starz@umbc.edu.
authors.forename: Michelle
authors.initials: M
authors.lastname: Starz-Gaiano
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D025461:Feedback, Physiological; D053263:Gene Regulatory Networks; D008297:Male; D008954:Models, Biological; D050791:STAT Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013737:Testis / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; C108529:apt protein, Drosophila
keywords: Apontic; Drosophila; JAK/STAT signaling; Stem cells; Testes somatic stem cells