2. Academic Validation
  3. Amputation Triggers Long-Range Epidermal Permeability Changes in Evolutionarily Distant Regenerative Organisms

Amputation Triggers Long-Range Epidermal Permeability Changes in Evolutionarily Distant Regenerative Organisms

  • bioRxiv. 2024 Aug 31:2024.08.29.610385. doi: 10.1101/2024.08.29.610385.
Kelly E Dooling 1,  Ryan T Kim 1,  Elane M Kim 1,  Erica Chen 1,  Adnan Abouelela 1,  Benjamin J Tajer 1,  Noah J Lopez 1,  Julia C Paoli 1,  Connor J Powell 1,  Anna G Luong 1,  S Y Celeste Wu 1,  Kara N Thornton 1,  Hani D Singer 1,  Aaron M Savage 1,  Joel Bateman 2,  Tia DiTommaso 2,  Duygu Payzin-Dogru 1,  Jessica L Whited 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Ave., Cambridge, MA, USA 02138.
  • 2 Brigham Regenerative Medicine Center and Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA, USA 02138.
  • 3 The Broad Institute of Harvard and MIT, Cambridge, MA, USA 02138.
  • 4 Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA 02138.
PMID: 39257748 DOI: 10.1101/2024.08.29.610385
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.

Keywords

MAPK signaling; epidermal barrier function; regeneration responses.

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