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 lacking Fibroblast growth factor 9 (Fgf9), demonstrating a novel role for FGF signaling in testicular embryogenesis. Fgf9(-/-) mice also exhibit lung hypoplasia and die at birth. Reproductive system phenotypes range from testicular hypoplasia to complete sex reversal, with most Fgf9(-/-) XY reproductive systems appearing grossly female at birth. Fgf9 appears to act downstream of Sry to stimulate mesenchymal proliferation, mesonephric cell migration, and Sertoli cell differentiation in the embryonic testis. While Sry is found only in some mammals, Fgfs are highly conserved. Thus, Fgfs may function in sex determination and reproductive system development in many species.
Colvin
J S
JS
Department of Molecular Biology and, Pharmacology, Washington University Medical School, Campus Box 8103, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Green
R P
RP
Schmahl
J
J
Capel
B
B
Ornitz
D M
DM
D000818:Animals; D012734:Disorders of Sex Development; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005836:Genitalia, Female / Q000196:embryology*; D005837:Genitalia, Male / Q000196:embryology*; D006609:High Mobility Group Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000196:embryology; D015183:Restriction Mapping; D055758:SOX9 Transcription Factor; D012733:Sex Differentiation / Q000235:genetics; D013737:Testis / Q000002:abnormalities / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics
C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D005346:Fibroblast Growth Factors