Reptin and pontin antagonistically regulate heart growth in zebrafish embryos.
Organ size is precisely regulated during development, but the control mechanisms remain obscure. We have isolated a mutation in zebrafish, liebeskummer (lik), which causes development of hyperplastic embryonic hearts. lik encodes Reptin, a component of a DNA-stimulated ATPase complex. The mutation activates ATPase activity of Reptin complexes and causes a cell-autonomous proliferation of cardiomyocytes to begin well after progenitors have fashioned the primitive heart tube. With regard to heart growth, beta-catenin and Pontin, a DNA-stimulated ATPase that is often part of complexes with Reptin, are in the same genetic pathways. Pontin reduction phenocopies the cardiac hyperplasia of the lik mutation. Thus, the Reptin/Pontin ratio serves to regulate heart growth during development, at least in part via the beta-catenin pathway.
Rottbauer
Wolfgang
W
Cardiovascular Research Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
Saurin
Andrew J
AJ
Lickert
Heiko
H
Shen
Xuetong
X
Burns
C Geoff
CG
Wo
Z Galen
ZG
Kemler
Rolf
R
Kingston
Robert
R
Wu
Carl
C
Fishman
Mark
M
D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006332:Cardiomegaly / Q000196:embryology / Q000209:etiology / Q000235:genetics; D002352:Carrier Proteins; D002455:Cell Division; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000502:physiology; D004625:Embryo, Nonmammalian; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006360:Heat-Shock Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D017354:Point Mutation; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D029961:Zebrafish Proteins; D051176:beta Catenin; C495269:ctnnb1 protein, zebrafish; C471329:ruvbl1 protein, zebrafish; C471327:ruvbl2 protein, zebrafish; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases; D000251:Adenosine Triphosphatases