title: Stem cells signal to the niche through the Notch pathway in the Drosophila ovary.
abstract: Stem cells are maintained and retain their capacity to continue dividing because of the influence of a niche. Although niches are important to maintain "stemness" in a wide variety of tissues, control of these niches is poorly understood. The Drosophila germline stem cells (GSCs) reside in a somatic cell niche. We show that Notch activation can induce the expression of niche-cell markers even in an adult fly; overexpression of Delta in the germline, or activated Notch in the somatic cells, results in extra niche cells, up to 10-fold over the normal number. In turn, these ectopic niche cells induce ectopic GSCs. Conversely, when GCSs do not produce functional Notch ligands, Delta and Serrate, the TGF-beta pathway is not activated in the GSCs, and they differentiate and subsequently leave the niche. Importantly, clonal analysis reveals that the receiving end of the Notch pathway is required in the somatic cells. These data show that a feedback loop exists between the stem cells and niche cells. Demonstration that stem cells can contribute to niche function has far-reaching consequences for stem cell therapies and may provide insight into how cancer can spread throughout an organism via populations of cancer stem cells.
authors.affiliation: Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, School of Medicine, Box 357350, 1959 NE Pacific Street, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Ward
authors.forename: Halyna R
authors.initials: HR
authors.lastname: Shcherbata
authors.forename: Steven H
authors.initials: SH
authors.lastname: Reynolds
authors.forename: Karin A
authors.initials: KA
authors.lastname: Fischer
authors.forename: Steven D
authors.initials: SD
authors.lastname: Hatfield
authors.forename: Hannele
authors.initials: H
authors.lastname: Ruohola-Baker
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology*; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000502:physiology; D010053:Ovary / Q000502:physiology*; D051880:Receptors, Notch / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; D016212:Transforming Growth Factor beta; C064045:delta protein