Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals.
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.
Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA.
Thomas R
0000-0001-9868-9704
TR
Gawriluk
Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA.
Jennifer
J
Simkin
Department of Statistics, University of Kentucky, Lexington, Kentucky 40506, USA.
Katherine L
KL
Thompson
Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA.
Shishir K
SK
Biswas
Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA.
Zak
Z
Clare-Salzler
Department of Veterinary Anatomy and Physiology, University of Nairobi, PO Box 30197-00100, Nairobi, Kenya.
John M
JM
Kimani
Department of Veterinary Anatomy and Physiology, University of Nairobi, PO Box 30197-00100, Nairobi, Kenya.
Stephen G
SG
Kiama
Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA.
Jeramiah J
0000-0001-5333-5531
JJ
Smith
Odum School of Ecology, University of Georgia, Athens, Georgia 30602, USA.|Department of Infectious Disease, University of Georgia, Athens, Georgia 30602, USA.
Vanessa O
VO
Ezenwa
Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA.|Department of Veterinary Anatomy and Physiology, University of Nairobi, PO Box 30197-00100, Nairobi, Kenya.
Ashley W
AW
Seifert
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D004431:Ear, External / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D008297:Male; D008322:Mammals / Q000235:genetics / Q000502:physiology; D051379:Mice; D051189:Murinae; D011817:Rabbits; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*