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

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-Cre(ERT2), showed that this pathway functions throughout life. Thus, a principal physiologic role of the PI3K pathway is to control primordial follicle activation via Foxo3.

Pubmed ID: 18601916

Authors

  • John GB
  • Gallardo TD
  • Shirley LJ
  • Castrillon DH

Journal

Developmental biology

Publication Data

September 1, 2008

Associated Grants

  • Agency: NCRR NIH HHS, Id: K26 RR024196
  • Agency: NCRR NIH HHS, Id: K26 RR024196-02
  • Agency: NCRR NIH HHS, Id: K26RR024196
  • Agency: NICHD NIH HHS, Id: R01 HD048690
  • Agency: NICHD NIH HHS, Id: R01 HD048690-04
  • Agency: NICHD NIH HHS, Id: R01HD048690

Mesh Terms

  • Animals
  • Forkhead Transcription Factors
  • Mice
  • Oocytes
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases
  • Signal Transduction