Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Skin shedding and tissue regeneration in African spiny mice (Acomys)

Subjects

Abstract

Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture1,2. After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards3. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells4) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A. kempi and A. percivali exhibit skin autotomy and subsequent rapid healing.
Figure 2: Acomys skin is weak, tears easily, and during repair develops a porous ECM rich in collagen type III.
Figure 3: Acomys exhibit de novo hair follicle regeneration in wounded skin.
Figure 4: Acomys regenerate hair follicles, sebaceous glands, dermis, adipose tissue and cartilage in 4-mm ear punches.

Similar content being viewed by others

References

  1. Maginnis, T. L. The costs of autotomy and regeneration in animals: a review and framework for future research. Behav. Ecol. 17, 857–872 (2006)

    Article  Google Scholar 

  2. Shargal, E., Rath-Wolfson, L., Kronfeld, N. & Dayan, T. Ecological and histological aspects of tail loss in spiny mice (Rodentia: Muridae, Acomys) with a review of its occurrence in rodents. J. Zool. 249, 187–193 (1999)

    Article  Google Scholar 

  3. Bauer, A. M., Russell, A. P. & Shadwick, R. E. Mechanical properties and morphological correlates of fragile skin in gekkonid lizards. J. Exp. Biol. 145, 79–102 (1989)

    Google Scholar 

  4. Kragl, M. et al. Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460, 60–65 (2009)

    Article  ADS  CAS  Google Scholar 

  5. Dubost, G. & Gasc, J.-P. The process of total tail autotomy in the South-American rodent, Proechimys . J. Zool. 212, 563–572 (1987)

    Article  Google Scholar 

  6. Vogel, H. G. Correlation between tensile-strength and collagen content in rat skin — effect of age and cortisol treatment. Connect. Tissue Res. 2, 177–182 (1974)

    Article  CAS  Google Scholar 

  7. Seifert, A. W., Monaghan, J. R., Voss, S. R. & Maden, M. Skin regeneration in adult axolotls: a blueprint for scar-free healing in vertebrates. PLoS One 7, e32875 (2012)

    Article  ADS  CAS  Google Scholar 

  8. Dang, C. M. et al. Scarless fetal wounds are associated with an increased matrix metalloproteinase-to-tissue-derived inhibitor of metalloproteinase ratio. Plast. Reconstr. Surg. 111, 2273–2285 (2003)

    Article  Google Scholar 

  9. Soo, C. et al. Differential expression of matrix metalloproteinases and their tissue-derived inhibitors in cutaneous wound repair. Plast. Reconstr. Surg. 105, 638–647 (2000)

    Article  CAS  Google Scholar 

  10. Yannas, I. V. Tissue and Organ Regeneration in Adults (Springer, 2001)

    Google Scholar 

  11. McGowan, K. M. & Coulombe, P. A. Onset of keratin 17 expression coincides with the definition of major epithelial lineages during skin development. J. Cell Biol. 143, 469–486 (1998)

    Article  CAS  Google Scholar 

  12. Andl, T., Reddy, S. T., Gaddapara, T. & Millar, S. E. WNT signals are required for the initiation of hair follicle development. Dev. Cell 2, 643–653 (2002)

    Article  CAS  Google Scholar 

  13. DasGupta, R. & Fuchs, E. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126, 4557–4568 (1999)

    CAS  PubMed  Google Scholar 

  14. Botchkarev, V. A. & Sharov, A. A. BMP signaling in the control of skin development and hair follicle growth. Differentiation 72, 512–526 (2004)

    Article  CAS  Google Scholar 

  15. Driskell, R. R., Giangreco, A., Jensen, K. B., Mulder, K. W. & Watt, F. M. Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis. Development 136, 2815–2823 (2009)

    Article  CAS  Google Scholar 

  16. Billingham, R. E. & Russell, P. S. Incomplete wound contracture and the phenomenon of hair neogenesis in rabbits’ skin. Nature 177, 791–792 (1956)

    Article  ADS  CAS  Google Scholar 

  17. Breedis, C. Regeneration of hair follicles and sebaceous glands from the epithelium of scars in the rabbit. Cancer Res. 14, 575–579 (1954)

    CAS  PubMed  Google Scholar 

  18. Ito, M. et al. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447, 316–320 (2007)

    Article  ADS  CAS  Google Scholar 

  19. Vorontsova, M. A. & Liozner, L. D. Asexual propagation and Regeneration 377–379 (Pergamon, 1960)

    Google Scholar 

  20. Borgens, R. B. Mice regrow the tips of their foretoes. Science 217, 747–750 (1982)

    Article  ADS  CAS  Google Scholar 

  21. Muneoka, K., Allan, C. H., Yang, X., Lee, J. & Han, M. Mammalian regeneration and regenerative medicine. Birth Defects Res. C Embryo Today 84, 265–280 (2008)

    Article  CAS  Google Scholar 

  22. Clark, L. D., Clark, R. K. & Heber-Katz, E. A new murine model for mammalian wound repair and regeneration. Clin. Immunol. Immunopathol. 88, 35–45 (1998)

    Article  CAS  Google Scholar 

  23. Chalkley, D. T. A quantitative histological analysis of forelimb regeneration in Triturus viridescens . J. Morphol. 94, 21–70 (1954)

    Article  Google Scholar 

  24. Globus, M., Vethamany-Globus, S. & Lee, Y. C. Effect of apical epidermal cap on mitotic cycle and cartilage differentiation in regeneration blastemata in the newt, Notophthalmus viridescens . Dev. Biol. 75, 358–372 (1980)

    Article  CAS  Google Scholar 

  25. Neufeld, D. A. & Day, F. A. Perspective: a suggested role for basement membrane structures during newt limb regeneration. Anat. Rec. 246, 155–161 (1996)

    Article  CAS  Google Scholar 

  26. Calve, S., Odelberg, S. J. & Simon, H. G. A transitional extracellular matrix instructs cell behavior during muscle regeneration. Dev. Biol. 344, 259–271 (2010)

    Article  CAS  Google Scholar 

  27. Satoh, A., Makanae, A., Hirata, A. & Satou, Y. Blastema induction in aneurogenic state and Prrx-1 regulation by MMPs and FGFs in Ambystoma mexicanum limb regeneration. Dev. Biol 355, 263–274 (2011)

    Article  CAS  Google Scholar 

  28. Hinz, B. Formation and function of the myofibroblast during tissue repair. J. Invest. Dermatol. 127, 526–537 (2007)

    Article  CAS  Google Scholar 

  29. Gundersen, H. J. G. Notes on the estimation of the numerical density of arbitrary profiles: the edge effect. J. Microsc. 111, 219–223 (1977)

    Article  Google Scholar 

  30. Kiama, S. G., Maina, J. N., Bhattacharjee, J. & Weyrauch, K. D. Functional morphology of the pecten oculi in the nocturnal spotted eagle owl (Bubo bubo africanus), and the diurnal black kite (Milvus migrans) and domestic fowl (Gallus gallus var. domesticus): a comparative study. J. Zool. 254, 521–528 (2001)

    Article  Google Scholar 

  31. Weibel, E. R. Stereological Methods (Academic, 1979)

    Google Scholar 

Download references

Acknowledgements

We thank John Kahiro for assisting during materials testing and the Department of Mechanical Engineering, University of Nairobi, for use of their equipment. We thank John Kimani, Stanley Marete and Jackson Mugweru, for help with animal care and materials procurement in Nairobi, Ekiru Ekaran for field assistance, and Bernard Agwanda, Darcy Ogada, and Hillary Young for help with identification and natural history of Acomys. Conversations with Steve Takata and Truman Young drew our attention to this phenomenon.

Author information

Authors and Affiliations

Authors

Contributions

A.W.S., J.R.G., T.M.P. and M.M. formulated the research. A.W.S, M.G.S, M.M. and S.G.K., performed the research and analysed the data. A.W.S. wrote the manuscript and all authors discussed the results, commented on and edited the manuscript.

Corresponding author

Correspondence to Ashley W. Seifert.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-10 and Supplementary References. (PDF 28697 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seifert, A., Kiama, S., Seifert, M. et al. Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature 489, 561–565 (2012). https://doi.org/10.1038/nature11499

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature11499

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing