p38α MAPK regulates myocardial regeneration in zebrafish

Chris Jopling, Guillermo Suñè, Cristina Morera, Juan Carlos Izpisua Belmonte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Although adult mammals are unable to significantly regenerate their heart, this is not the case for a number of other vertebrate species. In particular, zebrafish are able to fully regenerate their heart following amputation of up to 20% of the ventricle. Soon after amputation, cardiomyocytes dedifferentiate and proliferate to regenerate the missing tissue. More recently, identical results have also been obtained in neonatal mice. Ventricular amputation of neonates leads to a robust regenerative response driven by the proliferation of existing cardiomyocytes in a similar manner to zebrafish. However, this ability is progressively lost during the first week of birth. The fact that adult zebrafish retain the capacity to regenerate their heart suggests that they either possess a unique regenerative mechanism, or that adult mammals lose/ inhibit this process. p38α MAPK has previously been shown to negatively regulate the proliferation of adult mammalian cardiomyocytes. We sought to determine whether a similar mechanism exists in adult zebrafish, and whether this needs to be overcome to allow regeneration to proceed. To determine whether p38α MAPK also regulates zebrafish cardiomyocytes in a similar manner, we generated conditional transgenic zebrafish in which either dominant-negative or active p38α MAPK are specifically expressed in cardiomyocytes. We found that active p38α MAPK but not dominant-negative p38α MAPK blocks proliferation of adult zebrafish cardiomyocytes and, consequently, heart regeneration as well. It appears that adult zebrafish cardiomyocytes share many characteristics with adult mammalian cardiomyocytes, including p38α MAPK-mediated cell cycle inhibition. These findings raise the possibility that zebrafish-like heart regeneration could be achieved in adult mammals.

Original languageEnglish (US)
Pages (from-to)1195-1201
Number of pages7
JournalCell Cycle
Issue number6
StatePublished - Mar 15 2012
Externally publishedYes

Bibliographical note

Funding Information:
212, 500 and 1,000 μM, respectively. Cells were then pelleted Work in the laboratory of J.C.I.B. was supported by grants from again and resuspended in plating medium (MEM, 5% FBS, 10 MICINN, Fundacion Cellex, IPSEN Foundation, The Leona M. mM BDM, 2 mM Glutamax, 100 U/ml penicillin and 100 μg/ml and Harry B. Helmsley Charitable Trust, The G. Harold and streptomycin). Cell preparations were plated onto collagen type I Leila Y. Mathers Charitable Foundation and Sanofi-Aventis.


  • Cardiomyocyte
  • Heart
  • Proliferation
  • Regeneration
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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