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

Dooling, K. E.; Kim, R. T.; Kim, E. M.; Chen, E.; Abouelela, A.; Tajer, B. J.; Lopez, N. J.; Paoli, J. C.; Powell, C. J.; Luong, A. G.; Wu, S. Y. C.; Thornton, K. N.; Singer, H. D.; Savage, A. M.; Bateman, J.; DiTommaso, T.; Payzin-Dogru, D.; Whited, J. L.

doi:10.1101/2024.08.29.610385

bioRxiv · 10.1101/2024.08.29.610385

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

Dooling, K. E.·Kim, R. T.·Kim, E. M.·Chen, E.·Abouelela, A.·Tajer, B. J.·Lopez, N. J.·Paoli, J. C.·Powell, C. J.·Luong, A. G.·Wu, S. Y. C.·Thornton, K. N.·Singer, H. D.·Savage, A. M.·Bateman, J.·DiTommaso, T.·Payzin-Dogru, D.·Whited, J. L.

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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 O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/610385v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@81b022org.highwire.dtl.DTLVardef@52c2e9org.highwire.dtl.DTLVardef@17a5f93org.highwire.dtl.DTLVardef@118b8f6_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Dooling, K. E., Kim, R. T., Kim, E. M., Chen, E., Abouelela, A., Tajer, B. J., Lopez, N. J., Paoli, J. C., Powell, C. J., Luong, A. G., Wu, S. Y. C., Thornton, K. N., Singer, H. D., Savage, A. M., Bateman, J., DiTommaso, T., Payzin-Dogru, D., Whited, J. L.. 2024-08-30. Amputation Triggers Long-Range Epidermal Permeability Changes in Evolutionarily Distant Regenerative Organisms. https://doi.org/10.1101/2024.08.29.610385

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