Male-to-female sex reversal in mice lacking fibroblast growth factor 9

Fgfs direct embryogenesis of several organs, including the lung, limb, and anterior pituitary. Here we report male-to-female sex reversal in mice lack ing Fibroblast growth factor 9 (Fgf9), demonstrating a novel role for FGF s ignaling in testicular embryogenesis. Fgf9(/-) mice also exhibit lung hypop lasia and die at birth. Reproductive system phenotypes range from testicula r hypoplasia to complete sex reversal, with most Fgf9(-/-) reproductive sys tems appearing grossly female at birth. Fgf9 appears to act downstream of S ly to stimulate mesenchymal proliferation, mesonephric cell migration, and Sertoli cell differentiation in the embryonic testis. While Sry is found on ly in some mammals, Fgfs are highly conserved. Thus, Fgfs may function in s ex determination and reproductive system development in many species.