Harada Masayo, Omori Akiko, Nakahara Chiaki, Nakagata Naomi, Akita Keiichi, Yamada Gen
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.
Dev Dyn. 2015 Jun;244(6):759-73. doi: 10.1002/dvdy.24277.
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.
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.
The current study suggests that spatiotemporally regulated FGF signaling plays tissue-specific roles in multiple processes of external genitalia development.
生殖结节（GT）作为外生殖器的原基，其发育过程包含多个方面，包括GT的生长、尿道管的形成以及尿道的上皮分化。GT由源自外侧中胚层的间充质、外胚层上皮和内胚层上皮（胚胎尿道上皮）组成。这三层组织协同发育GT。
在GT生长的初始阶段（E11.5）左右，在GT的间充质中检测到FGF信号。在尿道形成的早期阶段（E13.5）左右，在GT的三层组织中均检测到FGF信号。随后，FGF信号主要在尿道上皮中检测到（E14.5）。通过条件性Fgfr基因敲除方法揭示了FGF信号在GT发育中的组织特异性作用。早期GT中的间充质FGF信号对其生长是必需的。GT中的外胚层FGF信号对于外胚层和尿道上皮在其交界处的分化以形成合适的尿道管是必需的。GT中的内胚层FGF信号对于尿道上皮的分层和细胞黏附特性是必需的。
当前研究表明，时空调节的FGF信号在外生殖器发育的多个过程中发挥组织特异性作用。
