Depletion of zebrafish essential and regulatory myosin light chains reduces cardiac function through distinct mechanisms.
OBJECTIVE
Mutations in the essential myosin light chain (ELC) and regulatory myosin light chain (RLC) genes have been linked to sarcomeric hypertrophic cardiomyopathies in humans; however, the specific functions of the different myosin light chains during cardiogenesis in a vertebrate animal are not well understood.


RESULTS
Using zebrafish (Danio rerio) as a model organism, we have identified cmlc1 and cmlc2 as the main ELC and RLC orthologues, respectively, and have furthermore characterized their functions during cardiogenesis by morpholino technology. Depletion of either cmlc1 or cmlc2 using morpholino-modified antisense oligonucleotides leads to a disruption in sarcomere structure and compromises cardiac function as well, although through seemingly distinct mechanisms. While myosin still assembles into a novel rod-like structure in both morphants, the sarcomere length is longer in cmlc1 morphants than that in wild-type embryos, whereas it is shorter in cmlc2 morphants. In addition, cardiomyocyte size and number are increased upon depletion of cmlc1, resulting in a larger ventricular chamber volume; in contrast, depletion of cmlc2 leads to a reduction in cardiomyocyte size and number.


CONCLUSIONS
Our data have elucidated distinct roles for cmlc1 and cmlc2 during zebrafish cardiogenesis, suggesting that cardiomyopathies resulting from human mutations in ELCs vs. RLCs may have distinct pathological characteristics during disease progression.
Chen
Zhenyue
Z
Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Huang
Wei
W
Dahme
Tillman
T
Rottbauer
Wolfgang
W
Ackerman
Michael J
MJ
Xu
Xiaolei
X
D000818:Animals; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism*; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D048429:Cell Size; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D020320:Oligoribonucleotides, Antisense / Q000235:genetics; D012518:Sarcomeres / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
C532158:Cmlc1 protein, zebrafish; D018994:Myosin Light Chains; D020320:Oligoribonucleotides, Antisense; D029961:Zebrafish Proteins; C532159:myl7 protein, zebrafish; D024722:Cardiac Myosins