Irx4 identifies a chamber-specific cell population that contributes to ventricular myocardium development

Authors

  • Daryl O. Nelson,

    1. Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
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  • Dexter X. Jin,

    1. Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
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  • Karen M. Downs,

    1. Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
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  • Timothy J. Kamp,

    1. Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
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  • Gary E. Lyons

    Corresponding author
    1. Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
    • Correspondence to: Gary E. Lyons, Department of Cellular and Regenerative Biology, University of Wisconsin-Madison, 1300 University Avenue, SMI Room 319, Madison, WI 53706. E-mail: gelyons@facstaff.wisc.edu

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Abstract

Background: The ventricular myocardium is the most prominent layer of the heart, and the most important for mediating cardiac physiology. Although the ventricular myocardium is critical for heart function, the cellular hierarchy responsible for ventricle-specific myocardium development remains unresolved. Results: To determine the pattern and time course of ventricular myocardium development, we investigated IRX4 protein expression, which has not been previously reported. We identified IRX4+ cells in the cardiac crescent, and these cells were positive for markers of the first or second heart fields. From the onset of chamber formation, IRX4+ cells were restricted to the ventricular myocardium. This expression pattern persisted into adulthood. Of interest, we observed that IRX4 exhibits developmentally regulated dynamic intracellular localization. Throughout prenatal cardiogenesis, and up to postnatal day 4, IRX4 was detected in the cytoplasm of ventricular myocytes. However, between postnatal days 5–6, IRX4 translocated to the nucleus of ventricular myocytes. Conclusions: Given the ventricle-specific expression of Irx4 in later stages of heart development, we hypothesize that IRX4+ cells in the cardiac crescent represent the earliest cell population in the cellular hierarchy underlying ventricular myocardium development. Developmental Dynamics 243:381–392, 2014. © 2013 Wiley Periodicals, Inc.

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