Fgf10 mutant newts regenerate normal hindlimbs despite severe developmental defects

Creators: Suzuki, Miyuki; Okumura, Akinori; Chihara, Akane; Shibata, Yuki; Endo, Tetsuya; Teramoto, Machiko; Agata, Kiyokazu; Bronner, Marianne E.¹; Suzuki, Ken-ichi T.

1. California Institute of Technology

Abstract

In amniote limbs, Fibroblast Growth Factor 10 (FGF10) is essential for limb development, but whether this function is broadly conserved in tetrapods and/or involved in adult limb regeneration remains unknown. To tackle this question, we established Fgf10 mutant lines in the newt Pleurodeles waltl which has amazing regenerative ability. While Fgf10 mutant forelimbs develop normally, the hindlimbs fail to develop and downregulate FGF target genes. Despite these developmental defects, Fgf10 mutants were able to regenerate normal hindlimbs rather than recapitulating the embryonic phenotype. Together, our results demonstrate an important role for FGF10 in hindlimb formation, but little or no function in regeneration, suggesting that different mechanisms operate during limb regeneration versus development.

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Acknowledgement

We thank Profs. Toshinori Hayashi and Takashi Yamamoto in Hiroshima University and Takashi Takeuchi in Tottori University for providing newt and their great support. We also thank Profs. Hideyo Ohuchi in Okayama University and Yasuhiro Kamei in National Institute for Basic Biology for their advice and help. This work was supported by Japan Science and Technology Agency (JST), Core Research for Evolutionary Science and Technology (CREST), (JPMJCR2025 to K.T.S.), Japan Society for the Promotion of Science (JSPS), KAKENHI Grant-in-Aid for Scientific Research (B) (JP21H03829 to K.T.S.), Grant-in-Aid for JSPS Fellows (17J04796 to M.S.), Overseas Research Fellowships, Human Frontier Science Program Organization (HFSPO), Human Frontier Science Program (HFSP) Long Term Fellowship (LT0009/2022-L to M.S.), and NIH R35 (NS111564 to M.E.B.).

Contributions

M.S., M.E.B., and K.T.S. designed research; M.S., A.O., A.C., Y.S., M.T., and K.T.S. performed research; M.S., A.O., A.C., M.T., and K.T.S. contributed new reagents/analytic tools; M.S., A.O., A.C., M.T., and K.T.S. analyzed data; T.E., K.A., and M.E.B. supervision; K.T.S. project administration; and M.S., A.O., A.C., Y.S., T.E., M.T., K.A., M.E.B., and K.T.S. wrote the paper.

Data Availability

Sequencing data have been deposited in the NCBI BioProject (PRJDB15083) (20). All other data are included in the manuscript and/or SI Appendix.

Conflict of Interest

The authors declare no competing interest.

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