The role of p63 in embryonic external genitalia outgrowth in mice. (2nd February 2023)

• Record Type: Journal Article
• Authors: Tanaka, Kosei; Matsumaru, Daisuke; Suzuki, Kentaro; Yamada, Gen; Miyagawa, Shinichi
• Other Names: Ochi H. guestEditor.; Michiue T. guestEditor.; Kato T. guestEditor.; Zorn A. guestEditor.; Hayashi T. guestEditor.; Inoue T. guestEditor.; Kondo M. guestEditor.; Taira M. guestEditor.
• Is Part Of: Development growth and differentiation. Volume 65:Number 2(2023)
• Page Start: 132
• Page End: 140
• Publication Date: 2023-02-02
• Subjects: cloaca -- external genitalia -- Fgf8 -- hedgehog -- p63 -- Wnt; Embryology -- Periodicals; Developmental biology -- Periodicals; Growth -- Periodicals; 574.3
• DOI: 10.1111/dgd.12840
• Languages: English
• ISSNs: 0012-1592

Abstract

Abstract: Embryonic external genitalia (genital tubercle [GT]) protrude from the cloaca and outgrow as cloacal development progresses. Individual gene functions and knockout phenotypes in GT development have been extensively analyzed; however, the interactions between these genes are not fully understood. In this study, we investigated the role of p63, focusing on its interaction with the Shh–Wnt/Ctnnb1–Fgf8 pathway, a signaling network that is known to play a role in GT outgrowth. p63 was expressed in the epithelial tissues of the GT at E11.5, and the distal tip of the GT predominantly expressed the ΔNp63α isoform. The GTs in p63 knockout embryos had normal Shh expression, but CTNNB1 protein and Fgf8 gene expression in the distal urethral epithelium was decreased or lost. Constitutive expression of CTNNB1 in p63 ‐null embryos restored Fgf8 expression, accompanied by small bud structure development; however, such bud structures could not be maintained by E13.5, at which point mutant GTs exhibited severe abnormalities showing a split shape with a hemorrhagic cloaca. Therefore, p63 is a key component of the signaling pathway that triggers Fgf8 expression in the distal urethral epithelium and contributes to GT outgrowth by ensuring the structural integrity of the cloacal epithelia. Altogether, we propose that p63 plays an essential role in the signaling network for the development of external genitalia. Abstract : We investigated the role of p63 during embryonic external genitalia development. We found that p63 is a key component of the signaling pathway that triggers Fgf8 expression in the distal urethral epithelium and contributes to embryonic external genitalia outgrowth.