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<p>Hippo-Yap/Taz pathway is essential for tissue regeneration in multiple species. However, we found that in the highly regenerative salamanders, <i>Yap</i> knockout does not compromise the limb regeneration due to genetic compensation response (GCR). Specifically, the mutated <i>Yap</i> locus derived non-sense mRNA, which was recognized by UPF3A to instruct compensatory <i>Taz</i> induction. Blocking <i>Yap</i> mRNA or protein indeed inhibits regeneration. GCR could be utilized to maintain the robustness of limb regeneration.</p><p></p>

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Genetic compensation response contributes to Pleurodeles waltl limb regeneration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月31日

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  • Binxu Yin,
  • Changhao Yu,
  • Yang Liu,
  • Hao Cai,
  • Wencheng Wu,
  • Tingting Ye,
  • Lei Wang,
  • Lujia Xiao,
  • Yi Zhu,
  • Huaijuan Guo,
  • Kun Zhang,
  • Heng Wang

摘要

Hippo-Yap/Taz pathway is essential for tissue regeneration in multiple species. However, we found that in the highly regenerative salamanders, Yap knockout does not compromise the limb regeneration due to genetic compensation response (GCR). Specifically, the mutated Yap locus derived non-sense mRNA, which was recognized by UPF3A to instruct compensatory Taz induction. Blocking Yap mRNA or protein indeed inhibits regeneration. GCR could be utilized to maintain the robustness of limb regeneration.