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First published online 5 November 2003
doi: 10.1242/dev.00844
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1 Department of Molecular, Cell and Developmental Biology, University of
California, Los Angeles, Los Angeles, CA 90095, USA
2 Molecular Biology Institute, University of California, Los Angeles, Los
Angeles, CA 90095, USA
3 Jonsson Cancer Center, University of California, Los Angeles, Los Angeles, CA
90095, USA
4 Cardiovascular Research Laboratory, University of California, Los Angeles, Los
Angeles, CA 90095, USA
5 Department of Pediatrics, University of California, Los Angeles, Los Angeles,
CA 90095, USA
6 Developmental Biology Laboratory, Massachusetts General Hospital, Charlestown,
MA 02129, USA
7 Institute of Molecular and Cell Biology, College of Life Science, National
Taiwan University, Taipei, Taiwan
* Author for correspondence (e-mail: chenjn{at}mcdb.ucla.edu)
Accepted 29 August 2003
Na,K-ATPase is an essential gene maintaining electrochemical gradients
across the plasma membrane. Although previous studies have intensively focused
on the role of Na,K-ATPase in regulating cardiac function in the adults,
little is known about the requirement for Na,KATPase during embryonic heart
development. Here, we report the identification of a zebrafish mutant,
heart and mind, which exhibits multiple cardiac defects, including
the primitive heart tube extension abnormality, aberrant cardiomyocyte
differentiation, and reduced heart rate and contractility. Molecular cloning
reveals that the heart and mind lesion resides in the 
1B1
isoform of Na,K-ATPase. Blocking Na,K-ATPase 1B1 activity by
pharmacological means or by morpholino antisense oligonucleotides phenocopies
the patterning and functional defects of heart and mind mutant
hearts, suggesting crucial roles for Na,KATPase 1B1 in embryonic
zebrafish hearts. In addition to 1B1, the Na,K-ATPase 2 isoform
is required for embryonic cardiac patterning. Although the 1B1 and
2 isoforms share high degrees of similarities in their coding
sequences, they have distinct roles in patterning zebrafish hearts. The
phenotypes of heart and mind mutants can be rescued by supplementing
1B1, but not 2, mRNA to the mutant embryos,
demonstrating that 1B1 and 2 are not functionally equivalent.
Furthermore, instead of interfering with primitive heart tube formation or
cardiac chamber differentiation, blocking the translation of Na,KATPase
2 isoform leads to cardiac laterality defects.
Key words: Heart development, Zebrafish, Na, K-ATPase
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