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Scientists at the Institute of Molecular Biology identify key event for sex determination
Date:11/27/2012

Scientists at the Institute of Molecular Biology (IMB) in Mainz have identified a protein essential for initiating the development of male sex organs. Loss of the gene Gadd45g results in complete sex reversal of male mice, making them appear female. The researchers' finding uncovers a novel signaling cascade, which acts early in development to determine the gonads in males. This discovery sheds light on the genetic network that controls how embryos develop as males or females. The research has just been published in the high-impact journal Developmental Cell.

Research carried out in the laboratory of IMB Director Professor Christof Niehrs uncovered that the deletion of just one gene, Gadd45g, results in male mice with external genitalia that are indistinguishable from those of female mice. Furthermore, the internal reproductive organs of the mutant male mice look like those of females, indicating that a complete sex reversal has occurred. Says Christof Niehrs, "when breeding Gadd45g mutant mice we were puzzled why we got only females, until we discovered that some of these females actually carry a Y-chromosome."

The researchers further showed that Gadd45g exerts its effect by regulating signaling cascades that control the gene Sry, which had previously shown to be a master regulator of male sex development. This study both identifies a new role for Gadd45g and suggests a novel signaling pathway that could have important implications for research into disorders of sexual development.

For male sex organs to develop correctly, it is essential that the gene Sry is expressed at high levels within a very narrow timeframe in the embryo. The group of Christof Niehrs has now shown that Gadd45g is expressed in a pattern highly similar to that of Sry. The Gadd45g gene is, however, active just before Sry is turned on. Importantly, in mice lacking Gadd45g, the Sry gene is not expressed correctly. This indicates that Gadd45g controls the e
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Contact: Ralf Dahm
press@imb-mainz.de
49-613-139-21455
Johannes Gutenberg Universitaet Mainz
Source:Eurekalert

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