ZFIN ID: ZDB-PUB-120314-1
p38alpha MAPK regulates myocardial regeneration in zebrafish
Jopling, C., Suñe, G., Morera, C., and Izpisua Belmote, J.C.
Date: 2012
Source: Cell cycle (Georgetown, Tex.)   11(6): 1195-1201 (Journal)
Registered Authors: Jopling, Chris
Keywords: none
MeSH Terms:
  • Amputation
  • Animals
  • Animals, Genetically Modified/embryology
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/metabolism
  • Bromodeoxyuridine/metabolism
  • Cell Cycle Checkpoints
  • Cell Proliferation
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins/metabolism
  • Heart/physiology*
  • Histones/genetics
  • Histones/metabolism
  • Immunohistochemistry
  • Mitogen-Activated Protein Kinase 14/genetics
  • Mitogen-Activated Protein Kinase 14/metabolism*
  • Mitosis
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/drug effects
  • Myocytes, Cardiac/physiology
  • Recombination, Genetic
  • Regeneration*
  • Tamoxifen/pharmacology
  • Transgenes
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology*
PubMed: 22391208 Full text @ Cell Cycle

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 œAPK 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 œAPK also regulates zebrafish cardiomyocytes in a similar manner, we generated conditional transgenic zebrafish in which either dominant-negative or active p38α œAPK are specifically expressed in cardiomyocytes. We found that active p38α œAPK but not dominantnegative p38α œAPK 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.