title: Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind.
abstract: Normal self-renewal of follicle stem cells (FSCs) in the Drosophila ovary requires Hedgehog (Hh) signaling. Excess Hh signaling, induced by loss of patched (ptc), causes cell-autonomous duplication of FSCs. We have used a genetic screen to identify Mastermind (Mam), the Notch pathway transcriptional co-activator, as a rare dose-dependent modifier of aberrant FSC expansion induced by excess Hh. Complete loss of Mam activity severely compromises the persistence of both normal and ptc mutant FSCs, but does not affect the maintenance of ovarian germline stem cells. Thus, Mam, like Hh, is a crucial stem cell factor that acts selectively on FSCs in the ovary. Surprisingly, other Notch pathway components, including Notch itself, are not similarly required for FSC maintenance. Furthermore, excess Notch pathway activity alone accelerates FSC loss and cannot ameliorate the more severe defects of mam mutant FSCs. This suggests an unconventional role for Mam in FSCs that is independent of Notch signaling. Loss of Mam reduces the expression of a Hh pathway reporter in FSCs but not in wing discs, suggesting that Mam might enhance Hh signaling specifically in stem cells of the Drosophila ovary.
authors.affiliation: Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, NY 10027, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Vied
authors.forename: Daniel
authors.initials: D
authors.lastname: Kalderon
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000378:metabolism*; D004843:Epistasis, Genetic; D005260:Female; D017930:Genes, Reporter; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C085316:mam protein, Drosophila; C070844:ptc protein, Drosophila; C077245:hh protein, Drosophila