Expression patterns of Fgf8 and Shh in the developing external genitalia of Suncus murinus

Abstract

Reciprocal epithelial-mesenchymal interactions and several signalling pathways regulate the development of the genital tubercle (GT), an embryonic primordium of external genitalia. The morphology of the adult male external genitalia of the Asian house musk shrew Suncus murinus (hereafter, laboratory name: suncus) belonging to the order Eulipotyphla (the former order Insectivora or Soricomorpha) differs from those of mice and humans. However, the developmental process of the suncus GT and its regulatory genes are unknown. In the present study, we explored the morphological changes and gene expression patterns during the development of the suncus GT. Morphological observations suggested the presence of common (during the initial outgrowth) and species-specific (during the sexual differentiation of GT) developmental processes of the suncus GT. In gene expression analysis, fibroblast growth factor 8 (Fgf8) and sonic hedgehog (Shh), an indicator and regulator of GT development in mice respectively, were found to be expressed in the cloacal epithelium and the developing urethral epithelium of the suncus GT. This pattern of expression specifically in GT epithelium is similar to that observed in the developing mouse GT. Our results indicate that the mechanism of GT formation regulated by the FGF and SHH signalling pathways is widely conserved in mammals.

New developments in the biology of fibroblast growth factors

“…Developmental gene expression patterns and mechanisms are conserved across species that diverge in external genitalia structure. For example, in both mouse and Asian house musk shrew ( Suncus murinus ) expression patterns of Fgf8 and Shh are similar in the genital tubercle epithelium (Miyado et al, 2017). Consistent with FGF8 signaling to mesenchymal FGFRs, tissue‐specific inactivation of Fgfr2 shows that mesenchymal FGF signaling in the early‐stage genital tubercle is required for its outgrowth (Gredler et al, 2015; Harada et al, 2015).…”

Differential cell proliferation and cell death during the urethral groove formation in guinea pig model

“…Shh mRNA is strongly expressed in endoderm-derived urethral epithelium of multiple species 12,[21][22][23][24] and Shh plays important roles in GT outgrowth, regulation of cell survival, and cell cycle. 18,19,25,26 In mice, Shh expression domain in distal and middle of the GT is retained in urethral epithelium which is restricted to the inside of GT, and only shifts out to the ventral surface of GT at urethral opening site in proximal ( Fig.…”

Spatiotemporal map of key signaling factors during early penis development

“…At E15.5, Shh continues to be expressed throughout the urethral and UPE, though in transverse view Shh is most highly expressed in the dorsal population of UPE cells 3,25 . High Shh expression continues to be observed in the developing preputial glands, a pattern continuing through E17.5 onwards 25,26 …”

“…3,25 High Shh expression continues to be observed in the developing preputial glands, a pattern continuing through E17.5 onwards. 25,26 Recently, an additional member of the HH family-Indian hedgehog (Ihh)-has been implicated in external genital development and its expression pattern is beginning to be characterized. One study showed that Ihh mRNA localizes to the epithelial cells of the urethra, prepuce, and glans at E17, with expression higher in the male GT than in females.…”