hoxc12/c13 as key regulators for rebooting the developmental program in Xenopus limb regeneration

Aiko Kawasumi-Kita, Sang-Woo Lee, Daisuke Ohtsuka, Kaori Niimi, Yoshifumi Asakura, Keiichi Kitajima, Yuto Sakane, Koji Tamura, Haruki Ochi, Ken-ichi T. Suzuki and Yoshihiro Morishita ()
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Aiko Kawasumi-Kita: RIKEN Center for Biosystems Dynamics Research
Sang-Woo Lee: RIKEN Center for Biosystems Dynamics Research
Daisuke Ohtsuka: RIKEN Center for Biosystems Dynamics Research
Kaori Niimi: RIKEN Center for Biosystems Dynamics Research
Yoshifumi Asakura: RIKEN Center for Biosystems Dynamics Research
Keiichi Kitajima: RIKEN Center for Biosystems Dynamics Research
Yuto Sakane: Hiroshima University, Higashihiroshima
Koji Tamura: Tohoku University
Haruki Ochi: Yamagata University
Ken-ichi T. Suzuki: Hiroshima University, Higashihiroshima
Yoshihiro Morishita: RIKEN Center for Biosystems Dynamics Research

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract During organ regeneration, after the initial responses to injury, gene expression patterns similar to those in normal development are reestablished during subsequent morphogenesis phases. This supports the idea that regeneration recapitulates development and predicts the existence of genes that reboot the developmental program after the initial responses. However, such rebooting mechanisms are largely unknown. Here, we explore core rebooting factors that operate during Xenopus limb regeneration. Transcriptomic analysis of larval limb blastema reveals that hoxc12/c13 show the highest regeneration specificity in expression. Knocking out each of them through genome editing inhibits cell proliferation and expression of a group of genes that are essential for development, resulting in autopod regeneration failure, while limb development and initial blastema formation are not affected. Furthermore, the induction of hoxc12/c13 expression partially restores froglet regenerative capacity which is normally very limited compared to larval regeneration. Thus, we demonstrate the existence of genes that have a profound impact alone on rebooting of the developmental program in a regeneration-specific manner.

Date: 2024
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DOI: 10.1038/s41467-024-47093-y

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