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Proliferation of embryonic cardiomyocytes in zebrafish requires the sodium channel scn5Lab
Author(s) -
Bennett J.S.,
Stroud D.M.,
Becker J.R.,
Roden D.M.
Publication year - 2013
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.22400
Subject(s) - morpholino , zebrafish , myocyte , heart development , gene knockdown , embryonic stem cell , biology , cardiac myocyte , embryonic heart , microbiology and biotechnology , embryo , medicine , sodium channel , endocrinology , chemistry , sodium , genetics , cell culture , organic chemistry , gene
In mice, homozygous deletion of the cardiac sodium channel Scn5a results in defects in cardiac morphology and embryonic death before robust sodium current can be detected. In zebrafish, morpholino knockdown of cardiac sodium channel orthologs scn5Laa and scn5Lab perturbs specification of precardiac mesoderm and inhibits growth of the embryonic heart. It is not known which developmental processes are perturbed by sodium channel knockdown and whether reduced cell number is from impaired migration of cardiac progenitors into the heart, impaired myocyte proliferation, or both. We found that embryos deficient in scn5Lab displayed defects in primary cardiogenesis specific to loss of nkx2.5, but not nkx2.7 . We generated kaede reporter fish and demonstrated that embryos treated with anti‐ scn5Lab morpholino showed normal secondary differentiation of cardiomyocytes at the arterial pole between 30 and 48 h post‐fertilization. However, while proliferating myocytes were readily detected at 48 hpf in wild type embryos, there were no BrdU‐positive cardiomyocytes in embryos subjected to anti‐ scn5Lab treatment. Proliferating myocytes were present in embryos injected with anti‐ tnnt2 morpholino to phenocopy the silent heart mutation, and absent in embryos injected with anti‐ tnnt2 and anti ‐scn5Lab morpholinos, indicating cardiac contraction is not required for the loss of proliferation. These data demonstrate that the role of scn5Lab in later heart growth does not involve contribution of the secondary heart field, but rather proliferation of cardiomyocytes, and appears unrelated to the role of the channel in cardiac electrogenesis. genesis 51:562–574. © 2013 Wiley Periodicals, Inc.