
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.29.610385
preprint
2
Article
Amputation Triggers Long-Range Epidermal Permeability Changes in Evolutionarily Distant Regenerative Organisms
Dooling Kelly E. http://orcid.org/0009-0002-5029-7220

Kim Ryan T. http://orcid.org/0009-0007-3920-4982

Kim Elane M. http://orcid.org/0009-0002-7864-380X

Chen Erica http://orcid.org/0009-0000-7273-2081

Abouelela Adnan http://orcid.org/0009-0007-8811-0800

Tajer Benjamin J. http://orcid.org/0000-0001-7791-1249

Lopez Noah J. http://orcid.org/0000-0001-7005-298X

Paoli Julia C. http://orcid.org/0000-0001-8266-1766

Powell Connor J. http://orcid.org/0009-0006-6889-0099

Luong Anna G. http://orcid.org/0009-0003-0205-2146

Wu S.Y. Celeste http://orcid.org/0009-0008-3275-6052

Thornton Kara N. http://orcid.org/0009-0006-8248-7589

Singer Hani D. http://orcid.org/0009-0001-7722-2758

Savage Aaron M. http://orcid.org/0000-0002-2636-6145

Bateman Joel
DiTommaso Tia
Payzin-Dogru Duygu http://orcid.org/0000-0002-3717-0244

Whited Jessica L. http://orcid.org/0000-0002-3709-6515

31 8 2024
2024.08.29.610385https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.29.610385
nihpp-2024.08.29.610385.pdf
ABSTRACT

Previous studies have reported that amputation invokes body-wide responses in regenerative organisms, but most have not examined the implications of these changes beyond the region of tissue regrowth. Specifically, long-range epidermal responses to amputation are largely uncharacterized, with research on amputation-induced epidermal responses in regenerative organisms traditionally being restricted to the wound site. Here, we investigate the effect of amputation on long-range epidermal permeability in two evolutionarily distant, regenerative organisms: axolotls and planarians. We find that amputation triggers a long-range increase in epidermal permeability in axolotls, accompanied by a long-range epidermal downregulation in MAPK signaling. Additionally, we provide functional evidence that pharmacologically inhibiting MAPK signaling in regenerating planarians increases long-range epidermal permeability. These findings advance our knowledge of body-wide changes due to amputation in regenerative organisms and warrant further study on whether epidermal permeability dysregulation in the context of amputation may lead to pathology in both regenerative and non-regenerative organisms.

GRAPHICAL ABSTRACT
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