title: FGF8 is essential for formation of the ductal system in the male reproductive tract.
abstract: During development of the urogenital tract, fibroblast growth factor 8 (Fgf8) is expressed in mesonephric tubules, but its role in this tissue remains undefined. An evaluation of previously generated T-Cre-mediated Fgf8-deficient mice (T-Cre; Fgf8(flox/Δ2,3) mice), which lack Fgf8 expression in the mesoderm, revealed that the cranial region of the Wolffian duct degenerated prematurely and the cranial mesonephric tubules were missing. As a result, the epididymis, vas deferens and efferent ductules were largely absent in mutant mice. Rarb2-Cre was used to eliminate FGF8 from the mesonephric tubules but to allow expression in the adjacent somites. These mutants retained the cranial end of the Wolffian duct and formed the epididymis and vas deferens, but failed to elaborate the efferent ductules, indicating that Fgf8 expression by the mesonephric tubules is required specifically for the formation of the ductules. Ret knockout mice do not form the ureteric bud, a caudal outgrowth of the Wolffian duct and progenitor for the collecting duct network in the kidney, but they do develop the cranial end normally. This indicates that Fgf8, but not Ret, expression is essential to the outgrowth of the cranial mesonephric tubules from the Wolffian duct and to the development of major portions of the sex accessory tissues in the male reproductive tract. Mechanistically, FGF8 functions upstream of Lhx1 expression in forming the nephron, and analysis of Fgf8 mutants similarly shows deficient Lhx1 expression in the mesonephric tubules. These results demonstrate a multifocal requirement for FGF8 in establishing the male reproductive tract ducts and implicate Lhx1 signaling in tubule elongation.
authors: Cancer and Developmental Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
authors: Jirouta
authors: J
authors: Kitagaki
authors: Yutaka
authors: Y
authors: Ueda
authors: Xuan
authors: X
authors: Chi
authors: Nirmala
authors: N
authors: Sharma
authors: Cynthia M
authors: CM
authors: Elder
authors: Erika
authors: E
authors: Truffer
authors: Frank
authors: F
authors: Costantini
authors: Mark
authors: M
authors: Lewandoski
authors: Alan O
authors: AO
authors: Perantoni
mesh_terms: D000818:Animals; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005837:Genitalia, Male / Q000254:growth & development* / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009399:Nephrons / Q000254:growth & development / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014566:Urogenital System / Q000254:growth & development / Q000378:metabolism; D014928:Wolffian Ducts / Q000254:growth & development* / Q000378:metabolism
chemical_list: C496457:Fgf8 protein, mouse; D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse