《Cell》亮点 让女人更“女人”的基因

　　

生物通报道，最新一期的Cell杂志发表了一篇有趣的研究性文章，一个基因的改变可轻松地改变生殖器官从女到男的转变，文章刊登在12月11日的Cell上，文章标题为：Somatic Sex Reprogramming of Adult Ovaries to Testes by FOXL2 Ablation。

 

文章的这一新发现认为，一个基因可决定成年小鼠的生殖器是雌或是雄，这个基因就是FOXL2，若将成年雌性小鼠的FOLX2敲除将导致卵巢突变为睾丸，并产生睾丸酮。可以说，FOLX2是维持雌性生殖器特征的基因，这可能为女性不孕不育的研究带来新的线索。

 

杜克大学医学中心的Blanche Capel（未参与本文研究）表示，这是一项很重要的发现，这个基因是参与性别发育的重要因子。

 

该文的通讯作者，欧盟分子生物学实验室的Mathias Treier教授介绍道，几年前，他与同事就已经克隆了Foxl2基因，它是一个位于常染色体上的转录因子，当他们把发育期间的小鼠Foxl2敲除后，刚刚开始发育的卵巢渐渐退化。深入研究发现Foxl2终身表达，研究者们于是认为这一基因可能与维持雌性特征有关。

 

在最近的实验中，科学家们发现，决定在雌性小鼠卵巢发育成熟后再敲除该基因，他们估计，成熟的卵巢可能逐渐退化。

 

然而，出乎意料之外的是，雌性小鼠的卵巢不但没有退化，反而进一步分化，继而变成了睾丸。这令研究者们十分的惊讶。并且，不仅卵巢这一器官转变为睾丸，卵母细胞这些也转变为睾丸细胞。

 

Treier于是猜测，Foxl2可能在小鼠发育期间和成年期间发挥的调控作用有所不同。在发育期间，小鼠的Wnt4信号会严格控制雌性小鼠的生殖器官发育，避免发育成雄性生殖器。但是，待雌性小鼠成年后，Wnt4信号被关闭，Foxl2终身表达，用于维持雌性卵巢的性特征。

 

据Treier介绍，缺失Foxl2的雌性小鼠仅改变卵巢特征，其他的性别特征不因此而发生改变。雌性小鼠在卵巢发生改变后的进一步变化还有待更深入的研究。

 

Treier表示，以往的经典理论认为，器官一定发育完成，就无法再发生改变，但是，我们的这一研究改变了这一信条。

（生物通 小茜）

生物通推荐原文检索

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.