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 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.
Mathias S Gierl, Wolfram H Gruhn, Annika von Seggern, Nicole Maltry and Christof Niehrs (2012). Gadd45g functions in male sex determination by promoting p38 signaling and Sry expression. Developmental Cell 23(5):1032-42
Johannes Gutenberg Universitaet Mainz: http://www.uni-mainz.de
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
With funding from the Defense Department, scientists have begun work on devices that would use electric pulses to realign a memory process gone awry
On Friday, the Food and Drug Administration released a vital set of numbers about the routine use of antibiotics …
Side order of veg with that mammoth leg? The Neanderthal diet was probably more varied than we think – using vegetables, herbs and different cooking techniques
An exoskeleton that enables movement and provides tactile feedback has helped eight paralysed people regain sensation and move previously paralysed muscles
A female western gray whale set a new record swimming from Russia to Mexico and back, a total of 13,988 miles, in 172 days
Scientists operating a remote-controlled vehicle about 2,000 feet below water get a rare glimpse of a sperm whale. CBSN's Vladimir Duthiers and Elaine Quijano report on the video.
According to the experts, "blinking is like a kitty kiss"
Genetic profiling of cancer cells can help guide treatment, but such profiles can be ambiguous. Results would be more accurate if all labs tested normal cells from each patient, too.
Researchers in Kenya uncover tools dated to 3.3 million years ago, long before the first humans, as we know them, walked the Earth.
Researchers are facing up to methodological flaws that plague functional magnetic resonance imaging, but the interpretative problems might be harder to solve