Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth

George B. John, Teresa D. Gallardo, Lane J. Shirley, Diego H. Castrillon

Research output: Contribution to journalArticle

205 Scopus citations

Abstract

In mammals, oocytes are packaged into compact structures-primordial follicles-which remain inert for prolonged intervals until individual follicles resume growth via a process known as primordial follicle activation. Here we show that the phosphoinositide 3-kinase (PI3K) signalling pathway controls primordial follicle activation through the forkhead transcription factor Foxo3. Within oocytes, Foxo3 is regulated by nucleocytoplasmic shuttling. Foxo3 is imported into the nucleus during primordial follicle assembly, and is exported upon activation. Oocyte-specific ablation of Pten resulted in PI3K-induced Akt activation, Foxo3 hyperphosphorylation, and Foxo3 nuclear export, thereby triggering primordial follicle activation, defining the steps by which the PI3K pathway and Foxo3 control this process. Inducible ablation of Pten and Foxo3 in adult oocytes using a new tool for genetic analysis of the germline, Vasa-CreERT2, showed that this pathway functions throughout life. Thus, a principal physiologic role of the PI3K pathway is to control primordial follicle activation via Foxo3.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalDevelopmental Biology
Volume321
Issue number1
DOIs
StatePublished - Sep 1 2008

Keywords

  • Akt
  • Forkhead transcription factors
  • Germ cells
  • PI3K
  • Pten

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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