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

doi:10.1038/ncomms11164

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 journal › Article › peer-review

108 Scopus citations

Abstract

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 language	English
Article number	11164
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11164
State	Published - 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.

Funding

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.

Funders	Funder number
National Science Foundation Arctic Social Science Program
University of Kentucky
Office of International Science and Engineering	1353857, IOS-1353713
Directorate for Biological Sciences	1353857, 1353713

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/ncomms11164

Cite this

@article{d6cebdecbb0341119c717685608db797,

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

abstract = "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.",

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

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.",

year = "2016",

month = apr,

day = "25",

doi = "10.1038/ncomms11164",

language = "English",

volume = "7",

}

TY - JOUR

T1 - Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals

AU - Gawriluk, Thomas R.

AU - Simkin, Jennifer

AU - Thompson, Katherine L.

AU - Biswas, Shishir K.

AU - Clare-Salzler, Zak

AU - Kimani, John M.

AU - Kiama, Stephen G.

AU - Smith, Jeramiah J.

AU - Ezenwa, Vanessa O.

AU - Seifert, Ashley W.

N1 - 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.

PY - 2016/4/25

Y1 - 2016/4/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84964659738&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964659738&partnerID=8YFLogxK

U2 - 10.1038/ncomms11164

DO - 10.1038/ncomms11164

M3 - Article

C2 - 27109826

AN - SCOPUS:84964659738

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11164

ER -

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this