Kit signaling via PI3K promotes ovarian follicle maturation but is dispensable for primordial follicle activation

George B. John, Meredith J. Shidler, Peter Besmer, Diego H. Castrillon

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

In mammals, primordial follicles are generated early in life and remain dormant for prolonged intervals. Their growth resumes via a process known as primordial follicle activation. Recent genetic studies have demonstrated that phosphoinositide 3-kinase (PI3K) is the essential signaling pathway controlling this process throughout life, acting via Akt to regulate nucleocytoplasmic shuttling of Foxo3, which functions as a downstream molecular switch. The receptor tyrosine kinase Kit has been implicated by numerous studies as the critical upstream regulator of primordial follicle activation via PI3K/Akt. Here we present a genetic analysis of the contribution of Kit in regulating primordial follicle activation and early follicle growth, employing a knock-in mutation (KitY719F) that completely abrogates signaling via PI3K. Surprisingly, homozygous KitY719F female mice undergo primordial follicle activation and are fertile, demonstrating that Kit signaling via PI3K is dispensable for this process. However, other abnormalities were identified in KitY719F ovaries, including accelerated primordial follicle depletion and accumulation of morphologically abnormal primary/secondary follicles with persistent nuclear Foxo3 localization. These findings reveal specific roles of Kit in the maintenance of the primordial follicle reserve and in the primary to secondary follicle transition, but argue that Kit is dispensable in primordial follicle activation.

Original languageEnglish (US)
Pages (from-to)292-299
Number of pages8
JournalDevelopmental Biology
Volume331
Issue number2
DOIs
StatePublished - Jul 15 2009

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1-Phosphatidylinositol 4-Kinase
Ovarian Follicle
Receptor Protein-Tyrosine Kinases
Growth
Mammals
Ovary
Maintenance
Mutation

Keywords

  • Forkhead transcription factor
  • Foxo3
  • Imatinib
  • Kit
  • Oocyte
  • Ovary
  • PI3K
  • Primordial follicle

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Kit signaling via PI3K promotes ovarian follicle maturation but is dispensable for primordial follicle activation. / John, George B.; Shidler, Meredith J.; Besmer, Peter; Castrillon, Diego H.

In: Developmental Biology, Vol. 331, No. 2, 15.07.2009, p. 292-299.

Research output: Contribution to journalArticle

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