Scientists identify key event for sex determination

Nov 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 . Furthermore, the internal of the mutant male mice look like those of females, indicating that a complete sex reversal has occurred. Says Christof Niehrs, "when breeding Gadd45g 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 .

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 is not expressed correctly. This indicates that Gadd45g controls the expression of this master regulator and, in turn, male development.

The scientists also provide a possible mechanism by which Gadd45g regulates Sry. Their model suggests that Gadd45g binds to and activates key signaling proteins, such as p38, which activate the transcription factor Gata4. When active, this factor binds to and activates the Sry gene. Similar results are co-published in the same issue of Developmental Cell by the group of Andy Greenfield in the UK. "As outsiders to the field of sex determination we were surprised by how little was known about the regulation of Sry on the molecular level. Our work is a leap forward in the understanding of this fundamental process", says Niehrs.

Explore further: Genetic switch regulates a plant's internal clock based on temperature

More information: Gierl, M.S. et al. (2012), Gadd45g functions in male sex determination by promoting p38 signaling and Sry expression, Developmental Cell 23(5):1032-42. doi:10.1016/j.devcel.2012.09.014

add to favorites email to friend print save as pdf

Related Stories

Brain gene makes a female develop as a male

Dec 22, 2010

Australian scientists have discovered that changes to a gene involved in brain development can lead to testis formation and male genitalia in an otherwise female embryo.

Genetic tug of war determines gender

May 23, 2006

U.S. scientists says whether a mammalian egg develops into a male or female is determined by a struggle between genes encoding signaling proteins.

Ovaries must suppress their inner male

Dec 10, 2009

For an ovary to remain an ovary, the female organ has to continuously suppress its inner capacity to become male. That's the conclusion of a study in the December 11th issue of the journal Cell revealing that t ...

Recommended for you

Environmental pollutants make worms susceptible to cold

Sep 19, 2014

Some pollutants are more harmful in a cold climate than in a hot, because they affect the temperature sensitivity of certain organisms. Now researchers from Danish universities have demonstrated how this ...

User comments : 0