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bioRxiv · 10.1101/270652

Loss of embryonic neural crest cardiomyocytes causes adult hypertrophic cardiomyopathy

Abdul-Wajid, S.·Demarest, B.·Yost, H. J.
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Abstract

Neural crest cells migrate to the embryonic heart and transform into a small number of cardiomyocytes, but their functions in the developing and adult heart are unknown. Here, we map the fates of neural crest derived cardiomyocytes (NC-Cms) and genetically ablate them in embryogenesis in zebrafish. Specific NC-Cm ablation results in aberrant trabeculation patterns and altered Notch signaling, but is not detrimental to the development of the fish or early heart function. Strikingly, embryonic NC-Cm ablation results in adult fish that show severely hypertrabeculated hearts, altered cardiomyocyte size, diminished adult heart capacity and consequently poor physiological response to cardiac stress tests. Thus, we identify a novel developmental mechanism and genetic pathway that predisposes adults to hypertrophic cardiomyopathy and provides the first zebrafish model of adult-onset heart failure.

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Abdul-Wajid, S., Demarest, B., Yost, H. J.. 2018-02-23. Loss of embryonic neural crest cardiomyocytes causes adult hypertrophic cardiomyopathy. https://doi.org/10.1101/270652

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