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How axolotl cells ‘remember’ development to rebuild a lost limb

The molecular feedback loops that program positional identity as salamander limbs develop and regrow could be harnessed for regenerative medicine.
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  1. S. Y. Celeste Wu

    1. S. Y. Celeste Wu is in the Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

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  2. Jessica L. Whited

    1. Jessica L. Whited is in the Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

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Salamanders can regenerate full, functional limbs throughout life. The axolotl (Ambystoma mexicanum; Fig. 1) is one species of salamander that has been studied extensively in the hope that the molecular mechanisms that occur in nature could inspire therapeutic advances in regenerative medicine. Although it is valuable to understand how regenerative responses in axolotl tissue are initiated, it is equally important to consider how the patterning of regenerated structures is controlled to ensure a perfect match with what is missing. The positional identity of individual cells is a key facet of this consideration, because patterning decisions made at the cellular level underlie tissue-level organization. Writing in Nature , Otsuki et al. 1 investigate how cells ‘remember’ and sometimes rewire their positional identity during axolotl limb regeneration, elaborating on the role of the signalling protein Sonic hedgehog (Shh), a long-appreciated key player in limb growth. Specifically, the authors reveal a signalling feedback loop that is established when the animal first develops limbs and that is harnessed for regeneration later in life.

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doi: https://doi.org/10.1038/d41586-025-01447-8

References

  1. Otsuki, L., Plattner, S. A., Taniguchi-Sugiura, Y., Falcon, F. & Tanaka, E. M. Nature https://doi.org/10.1038/s41586-025-09036-5 (2025).

    Article  Google Scholar 

  2. Bryant, S. V. & Baca, B. A. J. Exp. Zool. 204, 307–323 (1978).

    Article  PubMed  Google Scholar 

  3. McCusker, C. D. & Gardiner, D. M. Dis. Model. Mech. 7, 593–599 (2014).

    Article  PubMed  Google Scholar 

  4. Roy, S. & Gardiner, D. M. J. Exp. Zool. 293, 186–190 (2002).

    Article  PubMed  Google Scholar 

  5. Johnson, G. L., Glasser, M. B., Charles, J. F., Duryea, J. & Lehoczky, J. A. Cell Rep. 41, 111701 (2022).

    Article  PubMed  Google Scholar 

  6. Clarke, J. D., Alexander, R. & Holder, N. Neurosci. Lett. 89, 1–6 (1988).

    Article  PubMed  Google Scholar 

  7. Flink, I. L. Anat. Embryol. (Berl.) 205, 235–244 (2002).

    Article  PubMed  Google Scholar 

  8. Kirsche, K. & Kirsche, W. Z. Mikrosk. Anat. Forsch. 71, 505–525 (1964).

    PubMed  Google Scholar 

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Competing Interests

The authors declare no competing interests.

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