Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals

Thomas R. Gawriluk, Jennifer Simkin, Katherine L. Thompson, Shishir K. Biswas, Zak Clare-Salzler, John M. Kimani, Stephen G. Kiama, Jeramiah J. Smith, Vanessa O. Ezenwa, Ashley W. Seifert

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Why mammals have poor regenerative ability has remained a long-standing question in biology. In regenerating vertebrates, injury can induce a process known as epimorphic regeneration to replace damaged structures. Using a 4-mm ear punch assay across multiple mammalian species, here we show that several Acomys spp. (spiny mice) and Oryctolagus cuniculus completely regenerate tissue, whereas other rodents including MRL/MpJ 'healer' mice heal similar injuries by scarring. We demonstrate ear-hole closure is independent of ear size, and closure rate can be modelled with a cubic function. Cellular and genetic analyses reveal that injury induces blastema formation in Acomys cahirinus. Despite cell cycle re-entry in Mus musculus and A. cahirinus, efficient cell cycle progression and proliferation only occurs in spiny mice. Together, our data unite blastema-mediated regeneration in spiny mice with regeneration in other vertebrates such as salamanders, newts and zebrafish, where all healthy adults regenerate in response to injury.

Original languageEnglish
Article number11164
JournalNature Communications
StatePublished - Apr 25 2016

Bibliographical note

Funding Information:
We thank Matt Snider, Zara Ashraf, Malik Guidry, John Ewoi and Stanley Marete for help with live-trapping, animal care and data collection. We thank Tiberius for reliable transport and Edward Scott for the gift of MRL/MpJ mice. We also thank Peter Jessel for kindly allowing us access to his property and for fruitful discussions. Funding for this work was provided by the National Science Foundation (NSF) and the Office for International Science and Engineering (OISE) to A.W.S. (IOS-1353713) and V.O.E. (IOS-1353857). Additional funding was provided to A.W.S. by the University of Kentucky.

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Physics and Astronomy (all)


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