Satoh Yoshihiko, Haraguchi Ryuma, Wright Tracy J, Mansour Suzanne L, Partanen Juha, Hajihosseini Mohammad K, Eswarakumar Veraragavan P, Lonai Peter, Yamada Gen
Center for Animal Resources and Development, Graduate School of Molecular and Genomic Pharmacy, Kumamoto University, 860-0811 Kumamoto, Japan.
Anat Embryol (Berl). 2004 Sep;208(6):479-86. doi: 10.1007/s00429-004-0419-9. Epub 2004 Aug 31.
Members of the fibroblast growth factor (FGF) family play diverse roles during the development and patterning of various organs. In human and mice, 22 FGFs and four receptors derived from several splice variants are present. Redundant expression and function of FGF genes in organogenesis have been reported, but their roles in embryonic external genitalia, genital tubercle (GT), development have not been studied in detail. To address the role of FGF during external genitalia development, we have analyzed the expression of FGF genes (Fgf8, 9, 10) and receptor genes (Fgfr1, r2IIIb, r2IIIc) in GT of mice. Furthermore, Fgf10 and Fgfr2IIIb mutant mice were analyzed to elucidate their roles in embryonic external genitalia development. Fgfr2IIIb was expressed in urethral plate epithelium during GT development. Fgfr2IIIb mutant mice display urethral dysmorphogenesis. Marker gene analysis for urethral plate and bilateral mesenchymal formation suggests the existence of epithelial-mesenchymal interaction during urethral morphogenesis. Therefore, FGF10/FGFR2IIIb signals seem to constitute a developmental cascade for such morphogenesis.
成纤维细胞生长因子（FGF）家族成员在各种器官的发育和模式形成过程中发挥着多种作用。在人类和小鼠中，存在22种FGF以及源自几种剪接变体的4种受体。已有报道称FGF基因在器官发生过程中存在冗余表达和功能，但它们在胚胎外生殖器、生殖结节（GT）发育中的作用尚未得到详细研究。为了探讨FGF在体外生殖器发育中的作用，我们分析了小鼠GT中FGF基因（Fgf8、9、10）和受体基因（Fgfr1、r2IIIb、r2IIIc）的表达。此外，对Fgf10和Fgfr2IIIb突变小鼠进行了分析，以阐明它们在胚胎外生殖器发育中的作用。Fgfr2IIIb在GT发育过程中于尿道板上皮中表达。Fgfr2IIIb突变小鼠表现出尿道发育异常。对尿道板和双侧间充质形成的标记基因分析表明尿道形态发生过程中存在上皮-间充质相互作用。因此，FGF10/FGFR2IIIb信号似乎构成了这种形态发生的发育级联反应。
