insulin-signalling pathway has a role in male differentiation.

The discovery of the role of Sry in male development was heralded as a great breakthrough and it became known as a classic master switch of development: XY vertebrates with functional Sry developed as males; those without it developed as females. Despite the initial excitement,however,working out what was upstream and downstream of this transcription factor proved very difficult. The insulin family signalling pathway comprises three receptors: Ir, Igf1r and Irr. Single mouse mutants at these loci do not show any abnormal sexual phenotype but, as the authors show by electron microscopy and histochemical analysis,XY triple mutants are completely feminized.
Despite the fact that sex determination mechanisms evolve rapidly, there is some degree of conservation in the pathways involved between invertebrates and vertebrates. As the insulin-signalling pathway is also present in worms and flies, Parada and colleagues call for using these organisms to identify further potential candidates in this pathway that have a role in male differentiation.
ORIGINAL RESEARCH PAPER
Nef, S. &Verma-Kurvari, S. et al. Testis determination requires insulin receptor family function in mice.
Nature 426, 291–295 (2003)
FURTHER READING Stadler, H. S. Modelling genitourinary defects in mice: an emerging genetic and developmental system. Nature Rev. Genet. 4, 478–482 (2003)