Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination.
Recently, we demonstrated that loss of Fgf9 results in a block of testis development and a male to female sex-reversed phenotype; however, the function of Fgf9 in sex determination was unknown. We now show that Fgf9 is necessary for two steps of testis development just downstream of the male sex-determining gene, Sry: (1) for the proliferation of a population of cells that give rise to Sertoli progenitors; and (2) for the nuclear localization of an FGF receptor (FGFR2) in Sertoli cell precursors. The nuclear localization of FGFR2 coincides with the initiation of Sry expression and the nuclear localization of SOX9 during the early differentiation of Sertoli cells and the determination of male fate.
Schmahl
Jennifer
J
Department of Cell Biology, Duke University, Durham, NC 27710, USA.
Kim
Yuna
Y
Colvin
Jennifer S
JS
Ornitz
David M
DM
Capel
Blanche
B
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000254:growth & development; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*; D012730:Sex Chromosomes; D019849:Sex Determination Processes; D012733:Sex Differentiation; D051876:Sex-Determining Region Y Protein; D013737:Testis / Q000166:cytology / Q000254:growth & development; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C496459:FGF9 protein, human; C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; C527933:Sox9 protein, mouse; C497746:Sry protein, mouse; D014157:Transcription Factors; D005346:Fibroblast Growth Factors; C496353:FGFR2 protein, human; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2