Sex Determination in Mammals
Yuna Kim, Akio Kobayashi, Ryohei Sekido, Leo DiNapoli, Jennifer Brennan, Marie-Christine Chaboissier, Francis Poulat, Richard R. Behringer, Robin Lovell-Badge, Blanche Capel. 2006. Fgf9 and Wnt4 Act as Antagonistic Signals to Regulate Mammalian Sex Determination. PLOS Biology, 4:6, p1000-1009.
Briefly tell us a bit about yourself, your career path over the years, and specifically what led you to begin working on sex determination in mammals.
At what particular stage in gonad development is the sex/gender of an organism determined to remain that particular gender? In other words, how plastic is primary and then secondary sex determination?
What threshold of Fgf9 signaling must be surpassed in order to commit the gonad to the male pathway? If this threshold is not met, does the gonad automatically commit to the female fate suggesting that female sex determination operates under a kind of “default” pathway?
In XY gonads, the Sry gene generates the initial signal that tips the balance between Wnt4 and Sox9/Fgf9 by up-regulating Sox9. In female gonads, what is the initial signal, if there is one, that tips the balance toward Wnt4 gene expression, and thus toward female sex development? Is there another signal that causes Wnt4 to be up-regulated and take control in female gonad development?
Is it possible (for example in the situation of a chimera) for Fgf9 and Wnt4 to be expressed so that they balance one another perfectly and are both equally expressed and inhibited? Conversely, what if neither Fgf9 nor Wnt4 is expressed, which sex type would develop? Has this research experience changed the way that you view sex and gender socially?
In your recent review article, “Balancing the bipotential gonad between alternative organ fates…”, you briefly discuss primary sex determination in other, non mammalian vertebrates. Are there any key differences between the pathways you found in mice and non mammals or between mice and human sex determination pathways? What do you see as the evolutionary history and evolved benefits of having sex determination based upon a genetic component rather than environmental cues, such as in alligators and frogs?
Currently in your opinion what are the most pressing questions in the field of sex determination, and what steps is your lab taking to address those questions?