Heart regeneration in zebrafish.
Cardiac injury in mammals and amphibians typically leads to scarring, with minimal regeneration of heart muscle. Here, we demonstrate histologically that zebrafish fully regenerate hearts within 2 months of 20% ventricular resection. Regeneration occurs through robust proliferation of cardiomyocytes localized at the leading epicardial edge of the new myocardium. The hearts of zebrafish with mutations in the Mps1 mitotic checkpoint kinase, a critical cell cycle regulator, failed to regenerate and formed scars. Thus, injury-induced cardiomyocyte proliferation in zebrafish can overcome scar formation, allowing cardiac muscle regeneration. These findings indicate that zebrafish will be useful for genetically dissecting the molecular mechanisms of cardiac regeneration.
Poss
Kenneth D
KD
Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA. kposs@enders.tch.harvard.edu
Wilson
Lindsay G
LG
Keating
Mark T
MT
D000818:Animals; D001777:Blood Coagulation; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D003094:Collagen / Q000032:analysis; D005337:Fibrin; D005355:Fibrosis; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D006335:Heart Injuries / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology / Q000601:surgery; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D016276:Ventricular Function; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins
D029961:Zebrafish Proteins; D005337:Fibrin; D003094:Collagen; C490545:ttk protein, zebrafish; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D001973:Bromodeoxyuridine