Copyright © 2009 Elsevier Inc.. All rights reserved.

Cell, Volume 139, Issue 6, 1130-1142, 11 December 2009

doi:10.1016/j.cell.2009.11.021

 

Somatic Sex Reprogramming of Adult Ovaries to Testes by FOXL2 Ablation

 

N. Henriette Uhlenhaut1, 7, Susanne Jakob2, Katrin Anlag1, Tobias Eisenberger1, Ryohei Sekido2, Jana Kress1, Anna-Corina Treier1, Claudia Klugmann1, Christian Klasen1, Nadine I. Holter1, Dieter Riethmacher3, Günther Schütz4, Austin J. Cooney5, Robin Lovell-Badge2 and Mathias Treier1, 6, , 

 

1 Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany

2 Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

3 Division of Human Genetics, School of Medicine, University of Southampton, Southampton SO16 6YD, UK

4 Division of Molecular Biology of the Cell I, German Cancer Research Center, D-69120 Heidelberg, Germany

5 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA

6 Medical Faculty, University of Cologne, D-50931 Cologne, Germany

Corresponding author

7 Present address: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA

 

【Summary】

In mammals, the transcription factor SRY, encoded by the Y chromosome, is normally responsible for triggering the indifferent gonads to develop as testes rather than ovaries. However, testis differentiation can occur in its absence. Here we demonstrate in the mouse that a single factor, the forkhead transcriptional regulator FOXL2, is required to prevent transdifferentiation of an adult ovary to a testis. Inducible deletion of Foxl2 in adult ovarian follicles leads to immediate upregulation of testis-specific genes including the critical SRY target gene Sox9. Concordantly, reprogramming of granulosa and theca cell lineages into Sertoli-like and Leydig-like cell lineages occurs with testosterone levels comparable to those of normal XY male littermates. Our results show that maintenance of the ovarian phenotype is an active process throughout life. They might also have important medical implications for the understanding and treatment of some disorders of sexual development in children and premature menopause in women.For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.