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Apoptosis in the developing mouse heart.

Laura Barbosky1, David K Lawrence, Ganga Karunamuni

  • 1Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-6011, USA.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|August 2, 2006
PubMed
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Cardiomyocyte apoptosis in the developing mouse heart outflow tract is crucial for normal heart development. This cell death process, similar to avian species, is linked to localized hypoxia and conserved across species.

Area of Science:

  • Developmental biology
  • Cardiovascular research
  • Cell death mechanisms

Background:

  • Apoptosis (programmed cell death) is frequent in the developing avian cardiac outflow tract (OFT).
  • Altering apoptosis levels causes defects similar to human conotruncal heart anomalies, highlighting its importance in heart morphogenesis.
  • Hypoxia in the OFT myocardium is implicated in regulating cell death and vasculogenesis.

Purpose of the Study:

  • To investigate if apoptosis occurs in the mouse heart outflow tract during comparable developmental stages as in avian species.
  • To determine if differential hypoxia is present in the murine OFT myocardium.

Main Methods:

  • Apoptosis detection using Lysotracker Red (LTR), a fluorescent vital dye.
  • Confirmation of apoptosis via Terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) and cleaved Caspase-3 immunostaining.

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  • Assessment of hypoxia using EF5 staining and HIF1alpha nuclear localization.

    • Main Results:

    • Apoptosis was observed in the mouse OFT myocardium from embryonic day (E) 12.5, peaking at E13.5-14.5.
    • High apoptosis levels were also found in ventricular apices and along the interventricular sulcus.
    • The OFT myocardium exhibited relative hypoxia and was surrounded by vasculature, mirroring findings in avian embryos.

    Conclusions:

    • Cardiomyocyte apoptosis is a conserved mechanism for normal outflow tract myocardial morphogenesis in both avian and mammalian species.
    • Regulated apoptosis and hypoxia play critical roles in heart development.
    • These findings provide insights into the evolutionary conservation of heart development processes.