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

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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.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8670, Japan

    Mitsuyuki Nakata, Keita Terui, Shugo Komatsu, Ryohei Shibata & Tomoro Hishiki

  2. Field of Human Disease Models, Major in Advanced Life Sciences and Medicine, Institute of Laboratory Animals, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Hiroaki Honda

  3. Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan

    Atsushi Iwama

  4. Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Atsushi Iwama

Authors
  1. Mitsuyuki Nakata
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  2. Hiroaki Honda
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  3. Atsushi Iwama
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  4. Keita Terui
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  5. Shugo Komatsu
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  6. Ryohei Shibata
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  7. Tomoro Hishiki
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Contributions

MN, HH, AI, KT, SK, RS, and TH performed the experiments, analyzed the data, and interpretated the results. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mitsuyuki Nakata.

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The authors have no conflict of interest to declare that are relevant to the content of this study.

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Nakata, M., Honda, H., Iwama, A. et al. Wnt5a plays a critical role in anal opening in mice at an early stage of embryonic development. Pediatr Surg Int 38, 743–747 (2022). https://doi.org/10.1007/s00383-022-05103-4

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  • DOI: https://doi.org/10.1007/s00383-022-05103-4

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