Fibroblast growth factor receptor 2 regulates proliferation and Sertoli differentiation during male sex determination.
Targeted mutagenesis of Fgf9 in mice causes male-to-female sex reversal. Among the four FGF receptors, FGFR2 showed two highly specific patterns based on antibody staining, suggesting that it might be the receptor-mediating FGF9 signaling in the gonad. FGFR2 was detected at the plasma membrane in proliferating coelomic epithelial cells and in the nucleus in Sertoli progenitor cells. This expression pattern suggested that Fgfr2 might play more than one role in testis development. To test the hypothesis that Fgfr2 is required for male sex determination, we crossed mice carrying a floxed allele of Fgfr2 with two different Cre lines to induce a temporal or cell-specific deletion of this receptor. Results show that deletion of Fgfr2 in embryonic gonads phenocopies deletion of Fgf9 and leads to male-to-female sex reversal. Using these two Cre lines, we provide the first genetic evidence that Fgfr2 plays distinct roles in proliferation and Sertoli cell differentiation during testis development.
Kim
Yuna
Y
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Bingham
Nathan
N
Sekido
Ryohei
R
Parker
Keith L
KL
Lovell-Badge
Robin
R
Capel
Blanche
B
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D017353:Gene Deletion; D015870:Gene Expression; D006609:High Mobility Group Proteins / Q000235:genetics; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000502:physiology*; D055758:SOX9 Transcription Factor; D012708:Sertoli Cells / Q000166:cytology*; D019849:Sex Determination Processes; D013737:Testis / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2; C045073:Cre recombinase; D019426:Integrases