title: Region-specific regulation of cell proliferation by FGF receptor signaling during the Wolffian duct development.
abstract: The Wolffian duct (WD) is a primordium of the male reproductive tract and kidney collecting duct system. Fibroblast growth factor receptors (FGFRs), members of the receptor tyrosine kinase (RTK) family, are essential for kidney development. Although the functions of FGFR signaling in kidney morphogenesis have been analyzed, their function in WD development has not been comprehensively investigated. Here, we demonstrate that Fgfr2 is the major Fgfr gene expressed throughout the WD epithelia and that it is essential for the maintenance of the WD, specifically in the caudal part of the WD. Hoxb7-Cre mediated inactivation of Fgfr2 in the mouse WD epithelia resulted in the regression of the caudal part of the WD and abnormal male reproductive tract development. Cell proliferation and expression of the downstream target genes of RTK signaling (Etv4 and Etv5) were decreased in the caudal part of the WD epithelia in the mutant embryos. Cranial (rostral) WD formation and ureteric budding were not affected. Ret, Etv4, and Etv5 expression were sustained in the ureteric bud of the mutant embryos. Taken together, these data suggest region-specific requirements for FGFR2 signaling in the developing caudal WD epithelia.
authors: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan; Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Osaka, Japan.
authors: Mika
authors: M
authors: Okazawa
authors: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
authors: Aki
authors: A
authors: Murashima
authors: Department of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo, Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku 113-8519, Tokyo, Japan.
authors: Masayo
authors: M
authors: Harada
authors: Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors: Naomi
authors: N
authors: Nakagata
authors: Laboratory for Lung Development, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuou-ku, Kobe 650-0047, Hyogo, Japan.
authors: Masafumi
authors: M
authors: Noguchi
authors: Laboratory for Lung Development, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuou-ku, Kobe 650-0047, Hyogo, Japan.
authors: Mitsuru
authors: M
authors: Morimoto
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Osaka, Japan.
authors: Tadashi
authors: T
authors: Kimura
authors: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: David M
authors: DM
authors: Ornitz
authors: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan. Electronic address: transg8@wakayama-med.ac.jp.
authors: Gen
authors: G
authors: Yamada
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006652:Histological Techniques; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008957:Models, Genetic; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014928:Wolffian Ducts / Q000196:embryology*
chemical_list: C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Cell proliferation; Fgfr; Receptor tyrosine kinase; Ret; Ureteric bud; Wolffian duct