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Clonally dominant cardiomyocytes direct heart morphogenesis

Nature volume 484, pages 479–484 (2012)Cite this article

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Abstract

As vertebrate embryos develop to adulthood, their organs undergo marked changes in size and tissue architecture. The heart acquires muscle mass and matures structurally to fulfil increasing circulatory needs, a process that is incompletely understood. Here we used multicolour clonal analysis to define the contributions of individual cardiomyocytes as the zebrafish heart undergoes morphogenesis from a primitive embryonic structure into its complex adult form. We find that the single-cardiomyocyte-thick wall of the juvenile ventricle forms by lateral expansion of several dozen cardiomyocytes into muscle patches of variable sizes and shapes. As juvenile zebrafish mature into adults, this structure becomes fully enveloped by a new lineage of cortical muscle. Adult cortical muscle originates from a small number of cardiomyocytes—an average of approximately eight per animal—that display clonal dominance reminiscent of stem cell populations. Cortical cardiomyocytes initially emerge from internal myofibres that in rare events breach the juvenile ventricular wall, and then expand over the surface. Our results illuminate the dynamic proliferative behaviours that generate adult cardiac structure, revealing clonal dominance as a key mechanism that shapes a vertebrate organ.

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Figure 1: Multicolour clonal labelling of embryonic zebrafish cardiomyocytes.
Figure 2: Several dozen embryonic cardiomyocytes build the juvenile ventricular wall.
Figure 3: Clonally dominant cortical cardiomyocytes.
Figure 4: Regeneration of cortical and primordial muscle after injury.
Figure 5: Origins of clonally dominant cardiomyocytes.

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Acknowledgements

We thank K. Kikuchi for generating cmlc2:CreER animals and for advice; J. Burris, A. Eastes, P. Williams and N. Blake for zebrafish care; A. Dickson for artwork; B. Hogan and Poss laboratory members for comments on the manuscript; and S. Johnson and Y. Gao for imaging advice. V.G. was supported by a National Heart, Lung, and Blood Institute (NHLBI) Medical Scientist Training Program supplement. K.D.P. is an Early Career Scientist of the Howard Hughes Medical Institute. This work was supported by grants from NHLBI (HL081674) and American Heart Association to K.D.P.

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Authors and Affiliations

  1. Department of Cell Biology and Howard Hughes Medical Institute, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Vikas Gupta & Kenneth D. Poss

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  1. Vikas Gupta
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  2. Kenneth D. Poss
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V.G. and K.D.P. designed experimental strategy, analysed data, and prepared the manuscript. V.G. performed all of the experiments.

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Correspondence to Kenneth D. Poss.

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The authors declare no competing financial interests.

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Gupta, V., Poss, K. Clonally dominant cardiomyocytes direct heart morphogenesis. Nature 484, 479–484 (2012). https://doi.org/10.1038/nature11045

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