Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation

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Item Type:	Article
Title:	Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation
Creators Name:	Uhlenhaut, N.H., Jakob, S., Anlag, K., Eisenberger, T., Sekido, R., Kress, J., Treier, A.C., Klugmann, C., Klasen, C., Holter, N.I., Riethmacher, D., Schütz, G., Cooney, A.J., Lovell-Badge, R. and Treier, M.
Abstract:	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.
Keywords:	Cell Transdifferentiation, Forkhead Box Protein L2, Forkhead Transcription Factors, Gene Deletion, Granulosa Cells, Oocytes, Ovary, Sertoli Cells, Testis, Animals, Mice
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	139
Number:	6
Page Range:	1130-1142
Date:	11 December 2009
Official Publication:	https://doi.org/10.1016/j.cell.2009.11.021
PubMed:	View item in PubMed

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