Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP-Dependent Proteases
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Adenosine Triphosphatases / chemistry
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Adenosine Triphosphatases / physiology
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Amino Acid Sequence
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Animals
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Base Sequence
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Cardiomegaly / embryology
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Cardiomegaly / etiology
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Cardiomegaly / genetics
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Carrier Proteins
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Cell Division
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Conserved Sequence
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Cytoskeletal Proteins / physiology
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Embryo, Nonmammalian
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Enzyme Activation
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Gene Expression Regulation, Developmental
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Heart / embryology*
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Heat-Shock Proteins / physiology
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Molecular Sequence Data
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Myocardium / cytology
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Myocardium / ultrastructure
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Point Mutation
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Sequence Homology, Amino Acid
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Serine Endopeptidases / physiology
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Trans-Activators / physiology
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Zebrafish
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Zebrafish Proteins / chemistry
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Zebrafish Proteins / genetics
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Zebrafish Proteins / physiology*
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beta Catenin
Substances
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Carrier Proteins
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Cytoskeletal Proteins
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Heat-Shock Proteins
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Nuclear Proteins
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Trans-Activators
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Zebrafish Proteins
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beta Catenin
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ctnnb1 protein, zebrafish
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ruvbl1 protein, zebrafish
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ruvbl2 protein, zebrafish
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ATP-Dependent Proteases
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Serine Endopeptidases
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Adenosine Triphosphatases
Associated data
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GENBANK/AY057075
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GENBANK/AY092764