title: Notch-dependent Fizzy-related/Hec1/Cdh1 expression is required for the mitotic-to-endocycle transition in Drosophila follicle cells.
abstract: During Drosophila oogenesis, Notch function regulates the transition from mitotic cell cycle to endocycle in follicle cells at stage 6. Loss of either Notch function or its ligand Delta (Dl) disrupts the normal transition; this disruption causes mitotic cycling to continue and leads to an overproliferation phenotype. In this context, the only known cell cycle component that responds to the Notch pathway is String/Cdc25 (Stg), a G2/M cell cycle regulator. We found that prolonged expression of string is not sufficient to keep cells efficiently in mitotic cell cycle past stage 6, suggesting that Notch also regulates other cell cycle components in the transition. By using an expression screen, we found such a component: Fizzy-related/Hec1/Cdh1 (Fzr), a WD40 repeat protein. Fzr regulates the anaphase-promoting complex/cyclosome (APC/C) and is expressed at the mitotic-to-endocycle transition in a Notch-dependent manner. Mutant clones of Fzr revealed that Fzr is dispensable for mitosis but essential for endocycles. Unlike in Notch clones, in Fzr mutant cells mitotic markers are absent past stage 6. Only a combined reduction of Fzr and ectopic Stg expression prolongs mitotic cycles in follicle cells, suggesting that these two cell cycle regulators, Fzr and Stg, are important mediators of the Notch pathway in the mitotic-to-endocycle transition.
authors.affiliation: Department of Biochemistry, University of Washington, J591 Health Science Building, Seattle, WA 98195-7350, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Schaeffer
authors.forename: Cassandra
authors.initials: C
authors.lastname: Althauser
authors.forename: Halyna R
authors.initials: HR
authors.lastname: Shcherbata
authors.forename: Wu-Min
authors.initials: WM
authors.lastname: Deng
authors.forename: Hannele
authors.initials: H
authors.lastname: Ruohola-Baker
mesh_terms: D000818:Animals; D064200:Cdh1 Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000502:physiology*; D010053:Ovary / Q000166:cytology*; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C577674:fzr protein, Drosophila; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila