title: Proliferation of embryonic cardiomyocytes in zebrafish requires the sodium channel scn5Lab.
abstract: 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.
authors: Program in Human Genetics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: J S
authors: JS
authors: Bennett
authors: D M
authors: DM
authors: Stroud
authors: J R
authors: JR
authors: Becker
authors: D M
authors: DM
authors: Roden
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D006321:Heart / Q000196:embryology; D000072576:Homeobox Protein Nkx-2.5; D009024:Morphogenesis; D060172:Morpholinos; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D060172:Morpholinos; D062554:NAV1.5 Voltage-Gated Sodium Channel; C528182:Nkx2.5 protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins
keywords: development; heart; myocardium; sodium channel
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