Wnt5a plays a critical role in anal opening in mice at an early stage of embryonic development

Abstract

Purpose: Anorectal malformations are associated with other organ malformations. Proximodistal elongation of the cloacal plate and anal opening at its distal end are essential for anal development. However, the anal developmental stage in which Wnt5a is directly involved remains unelucidated. Here, we attempted to identify this developmental stage; since Wnt5a is expressed in the mesoderm, and the striated muscle complex (SMC) in mice develops from the mesoderm, we also examined Wnt5a contribution to SMC development.

Methods: We established conditional knockout (CKO) mice in which Wnt5a could be knocked out using an appropriate tamoxifen dose. We evaluated the macroscopic appearance and histopathological features of Wnt5aCKO and wild-type mouse embryos.

Results: Wnt5aCKO mice showed phenotypes typical of Wnt5a constitutional knockout mice when Wnt5a was knocked out at E8-E11. Furthermore, the anus failed to open when Wnt5a was knocked out at E8 but opened when it was knocked out at E9 or thereafter. The caudal end of the SMC was dysplastic in Wnt5aCKO mice induced at E8, but was unaffected when mice were induced at E9 or thereafter.

Conclusion: We suggest a critical role for Wnt5a in anal opening and SMC formation at a very early stage of embryonic development.

Keywords: Anorectal malformations; Conditional knockout; Striated muscle complex; Wnt5a.