For over 250 years, biologists have been puzzled about why regenerative animals regrow lost appendages at a rate proportional to the degree of appendage loss. A team led by Dr. Chen-Hui Chen at the Institute of Cellular and Organismic Biology (ICOB) and Dr. Keng-Hui Lin at the Institute of Physics (IOP), Academia Sinica discovered a ‘mechanical wave’ that governs positional sensing during wound healing and regeneration. This study was published in Nature Physics in June 2023.
Highly regenerative animals can regrow lost appendages and the rate of regrowth is proportional to the amount of appendage loss. Curiosity about this century-old phenomenon prompted the team to investigate if the mechanism of wound healing, as the first stage of regeneration, determines the amputation position. In vitro studies revealed significant insights into the mechanics of the wound-healing process, including the identification of mechanical waves in post-injury epithelial cell expansion. It has been previously suggested that these mechanical waves may also be involved in positional sensing. The team performed live-cell imaging on adult zebrafish tailfins to monitor the collective migration of basal epithelial cells upon tailfin amputation. A cell density wave propagating away from the amputation edge was observed, with the maximum traveling a distance proportional to the amputation level and cell proliferation at later stages. Subsequent development of a mechanical model to explain this wave behavior, including the tension-dependent wave speed and amputation-dependent traveling distance, provided additional insights into the process. Together, the findings point to the presence of an in vivo positional sensing mechanism in regenerative tissue based on a coupling of mechanical signals manifested as a traveling density wave.
This study is supported by funding from the Institute of Cellular and Organismic Biology and the Institute of Physics, Academia Sinica, to C.-H.C. and K.-H.L.; grants from Academia Sinica to C.-H.C. (AS-CDA-109-L03) and the Academia Sinica Innovative Materials and Analytical Technology Exploration Program to K.-H.L. (AS-iMATE-109-12 and AS-iMATE-111-14); and grants from National Science and Technology Council, Taiwan, to C.-H.C. (MOST 106-2628-B-001-001-MY4 and MOST 110-2628-B-001-016), K.-H.L. (MOST 109-2122-M-001-001-MY2), and F.-L.W. (MOST 109-2112-M006-028-MY3).
Author list: Marco P. De Leon, Fu-Lai Wen, Giovanni J. Paylaga, Ying-Ting Wang, Hsiao-Yuh Roan, Chung-Han Wang, Chung-Der Hsiao, Keng-Hui Lin*, and Chen-Hui Chen*
Article title: Mechanical waves identify the amputation position during wound healing in the amputated zebrafish tailfin
Article link: https://www.nature.com/articles/s41567-023-02103-6
Dr. Chen-Hui Chen, Institute of Cellular and Organismic Biology, Academia Sinica
Dr. Keng-Hui Lin, Institute of Physics, Academia Sinica
Ms. Wen-Li Wang, Media Team, Secretariat, Central Administrative Office, Academia Sinica
Mr. Chang-Hung Chen, Media Team, Secretariat, Central Administrative Office, Academia Sinica
- The tailfin of an adult zebrafish. Epithelial cells are labeled by red fluorescence.
- The epithelial cells involved in the process of wound healing
- Zebrafish tailfin’s epithelial cells
- An interdisciplinary team led by Dr. Chen-Hui Chen at the Institute of Cellular and Organismic Biology and Dr. Keng-Hui Lin at the Institute of Physics, Academia Sinica