The Notch pathway is a highly conserved juxtacrine signaling mechanism that is important for many cellular processes during development, including differentiation and proliferation. Although Notch is important during ovarian follicle formation and early development, its functions during the gonadotropin-dependent stages of follicle development are largely unexplored. We observed positive regulation of Notch activity and expression of Notch ligands and receptors following activation of the luteinizing hormone-receptor in prepubertal mouse ovary. JAG1, the most abundantly expressed Notch ligand in mouse ovary, revealed a striking shift in localization from oocytes to somatic cells following hormone stimulation. Using primary cultures of granulosa cells, we investigated the functions of Jag1 using small interfering RNA knockdown. The loss of JAG1 led to suppression of granulosa cell differentiation as marked by reduced expression of enzymes and factors involved in steroid biosynthesis, and in steroid secretion. Jag1 knockdown also resulted in enhanced cell proliferation. These phenotypes were replicated, although less robustly, following knockdown of the obligate canonical Notch transcription factor RBPJ. Intracellular signaling analysis revealed increased activation of the mitogenic phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways following Notch knockdown, with a mitogen-activated protein kinase kinase inhibitor blocking the enhanced proliferation observed in Jag1 knockdown granulosa cells. Activation of YB-1, a known regulator of granulosa cell differentiation genes, was suppressed by Jag1 knockdown. Overall, this study reveals a role of Notch signaling in promoting the differentiation of preovulatory granulosa cells, adding to the diverse functions of Notch in the mammalian ovary.
Pubmed ID: 29126263 RIS Download
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This unknown targets IgG
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View all literature mentionsThis monoclonal targets Ybx1
View all literature mentionsThis monoclonal targets YB1 (D2B12) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-FoxO1 (Ser256)
View all literature mentionsThis monoclonal targets FoxO1 (C29H4) Rabbit mAb
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Human RBPJK
View all literature mentionsThis monoclonal targets Notch2 intracellular domain (human)
View all literature mentionsThis polyclonal targets GFP
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View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets Ybx1
View all literature mentionsThis monoclonal targets YB1 (D2B12) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-FoxO1 (Ser256)
View all literature mentionsThis monoclonal targets FoxO1 (C29H4) Rabbit mAb
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Human RBPJK
View all literature mentionsThis monoclonal targets Notch2 intracellular domain (human)
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets
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