Development of external genitalia (ExG) has been a topic of long mystery in the field of organogenesis research.

Early stage male and female of mouse embryos develop a common genital tubercle (GT) in the perineum whose outgrowth extends distally from the posterior cloacal regions. Concomitant with GT outgrowth, the cloaca is divided into urogenital sinus and anorectum by urorectal septum (URS) internally. The outgrowth of the GT is associated with the formation of endodermal epithelial urethral plate (UP) attached to the ventral epidermis of the GT. Such a common developmental phase is observed until around embryonic day 15.5 (E15.5) morphologically in mouse embryogenesis. Various growth factor genes, such as Fibroblast growth factor (Fgf) and Wnt genes are expressed and function during GT formation. Since the discovery of key growth factor signals and several regulatory molecules, elucidation of their functions has been achieved utilizing mouse developmental models, conditional gene knockout mouse and in vitro culture. Analyses on the phenotypes of such mouse models have revealed that several growth factor families play fundamental roles in ExG organogenesis based on the epithelial-mesenchymal interaction (EMI).

More recently, EMI between developing urethral epithelia and its bilateral mesenchyme of later stages is also reported during subsequent stage of androgen-dependent male-type urethral formation in the mouse embryo. Mafb, belonging to AP-1 family and a key androgen-responsive mesenchymal gene, is identified and starts to be expressed around E14.5 when masculinization of the urethra is initiated. Mesenchymal cell condensation and migration, which are regulated by nonmuscle myosin, are shown to be essential process for masculinization. Hence, studies on EMI at various embryonic stages are important not only for early but also for subsequent masculinization of the urethra. In this review, a dynamic mode of EMI for both early and late phases of ExG development is discussed.

外生殖器（ExG）的发展一直是器官发生研究领域的一个长期谜题。

小鼠胚胎的早期雌雄在会阴部发育出一个普通生殖器结节（GT），其结节从泄殖腔后部向远端延伸。伴随GT的生长，泄殖腔内部通过尿道隔（URS）分为泌尿生殖窦和肛门直肠。GT的生长与附着在GT腹侧表皮上的内皮上皮尿道板（UP）的形成有关。在小鼠胚胎发生中在形态学上一直观察到这种共同的发育阶段直到胚胎第15.5天（E15.5）左右。在GT形成过程中表达并发挥了各种生长因子基因，例如成纤维细胞生长因子（Fgf）和Wnt基因。由于发现了关键的生长因子信号和几个调节分子，体外培养。对此类小鼠模型的表型分析表明，基于上皮-间质相互作用（EMI），几种生长因子家族在ExG器官发生中起着基本作用。

最近，还报道了在小鼠胚胎中雄激素依赖性雄性型尿道形成的后续阶段中，发育中的尿道上皮细胞及其后期双侧间充质之间存在EMI。Mafb属于AP-1家族，是一个关键的雄激素反应性间充质基因，在开始男性化尿道时被鉴定并开始在E14.5周围表达。非肌肉肌球蛋白调节的间充质细胞凝结和迁移是男性化的基本过程。因此，在各个胚胎阶段进行EMI的研究不仅对于尿道的早期而且对于随后的男性化都很重要。在这篇综述中，讨论了ExG开发早期和后期的EMI动态模式。