Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation
Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation
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.
1130-1142
Uhlenhaut, N. Henriette
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Jacob, Susanne
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Anlag, Katrin
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Eisenberger, Tobias
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Sekido, Ryohei
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Kress, Jana
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Treier, Anna-Corina
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Klugmann, Claudia
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Klasen, Christian
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Holter, Nadine I.
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Riethmacher, Dieter
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Schütz, Günther
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Cooney, Austin J.
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Lovell-Badge, Robin
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Treier, Mathias
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11 December 2009
Uhlenhaut, N. Henriette
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Jacob, Susanne
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Anlag, Katrin
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Eisenberger, Tobias
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Sekido, Ryohei
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Kress, Jana
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Treier, Anna-Corina
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Klugmann, Claudia
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Klasen, Christian
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Holter, Nadine I.
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Riethmacher, Dieter
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Schütz, Günther
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Cooney, Austin J.
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Lovell-Badge, Robin
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Treier, Mathias
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Uhlenhaut, N. Henriette, Jacob, Susanne, Anlag, Katrin, Eisenberger, Tobias, Sekido, Ryohei, Kress, Jana, Treier, Anna-Corina, Klugmann, Claudia, Klasen, Christian, Holter, Nadine I., Riethmacher, Dieter, Schütz, Günther, Cooney, Austin J., Lovell-Badge, Robin and Treier, Mathias
(2009)
Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.
Cell, 139 (6), .
(doi:10.1016/j.cell.2009.11.021).
(PMID:20005806)
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.
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Submitted date: 19 July 2009
Published date: 11 December 2009
Organisations:
Human Genetics
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Local EPrints ID: 71591
URI: http://eprints.soton.ac.uk/id/eprint/71591
ISSN: 0092-8674
PURE UUID: 02cabf80-2576-4279-8112-4ba01e61fe40
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Date deposited: 15 Dec 2009
Last modified: 14 Mar 2024 02:53
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Contributors
Author:
N. Henriette Uhlenhaut
Author:
Susanne Jacob
Author:
Katrin Anlag
Author:
Tobias Eisenberger
Author:
Ryohei Sekido
Author:
Jana Kress
Author:
Anna-Corina Treier
Author:
Claudia Klugmann
Author:
Christian Klasen
Author:
Nadine I. Holter
Author:
Dieter Riethmacher
Author:
Günther Schütz
Author:
Austin J. Cooney
Author:
Robin Lovell-Badge
Author:
Mathias Treier
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