Figure 7.

Models. Epithelial cell fate decision in the lower FRT. Vaginal mesenchymal cells instruct vaginal epithelial cell fate in MDE by secreting BMP4, ActA, and FGF7/10. In MDE, BMP4 signal is transduced by canonical SMAD-dependent pathway, whereas ActA signal activates RUNX1 expression through a SMAD-independent pathway. FGF7/10 signal is transduced by the FGFR2IIIb-MAPK pathway in MDE. Three signaling pathways in concert activate expression of ΔNp63, and afterwards, the transcriptional activity of ΔNp63 locus is maintained by ΔNp63 itself (5). The disruption of one of these pathways interferes with ΔNp63 expression and subsequently cervical/vaginal epithelial differentiation, resulting in cervical and vaginal adenosis.