title: Tissue-specific roles of FGF signaling in external genitalia development.
abstract: BACKGROUND
  The developmental processes of the genital tubercle (GT), the anlage of the external genitalia, possess several developmental aspects, including GT outgrowth, urethral tube formation, and epithelial differentiation of the urethra. The GT comprises the mesenchyme derived from the lateral mesoderm, ectodermal epithelium, and endodermal epithelium (embryonic urethral epithelium). The three tissue layers develop the GT coordinately.
  
  
  RESULTS
  Around the initial stage of GT outgrowth (E11.5), FGF signaling was detected in the mesenchyme of the GT. FGF signaling was detected in the three tissue layers of the GT around the early stage of urethral formation (E13.5). Subsequently, FGF signaling was predominantly detected in the urethral epithelium (E14.5). Tissue-specific roles of FGF signaling in GT development were revealed by conditional Fgfr gene knockout approaches. Mesenchymal FGF signaling in the early-stage GT is required for its outgrowth. Ectodermal FGF signaling in the GT is required for the differentiation of the ectoderm and urethral epithelium at their junction to form the proper urethral tube. Endodermal FGF signaling in the GT is required for the stratification and cell adhesive characteristics of the urethral epithelium.
  
  
  CONCLUSIONS
  The current study suggests that spatiotemporally regulated FGF signaling plays tissue-specific roles in multiple processes of external genitalia development.
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.|Department of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Harada
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.|Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Omori
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakahara
authors.affiliation: Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.affiliation: Department of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Akita
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.|Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002448:Cell Adhesion; D002470:Cell Survival; D005260:Female; D005346:Fibroblast Growth Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005836:Genitalia, Female / Q000196:embryology* / Q000502:physiology; D005837:Genitalia, Male / Q000196:embryology* / Q000502:physiology; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism; D053823:Hedgehog Proteins / Q000502:physiology; D008297:Male; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014521:Urethra / Q000196:embryology / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology; D060449:Wnt Signaling Pathway
chemical_list: D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D011993:Recombinant Fusion Proteins; C465570:Shh protein, mouse; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: cell death; epithelial differentiation; genital tubercle; hypospadias; outgrowth; urethra