FRMD5 is essential for mammalian vaginal lumen formation through activating JAK2 - STAT3 signaling and inducing apoptosis
Vaginal lumen formation requires the timely activation of the epithelium apoptosis. However, the specific molecular mechanisms remain unclear. Here we found that urinary epithelium-specific knockout of Frmd5 induces longitudinal vaginal septum in postnatal mice. Depletion of FRMD5 impaired the apoptosis process and disrupted JAK2-STAT3 signaling activation in vaginal epithelium. Mechanistically, FRMD5 interacted with both JAK2 and STAT3 and strengthened the interaction between JAK2 and STAT3. This interaction was disrupted by loss of FRMD5, subsequently inhibiting STAT3 phosphorylation and activation. Furthermore, Frmd5 depletion transcriptionally downregulated Cas3 and Cas8 and upregulated Bcl2 and Bcl-xl expression. This study identified an essential role of Frmd5 in the regulation of vaginal epithelium apoptosis during vaginal formation in mice, which unveils a genetic mechanism for congenital vaginal developmental disorders.