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Related Experiment Videos

Serotonin 2B receptor is required for heart development.

C G Nebigil1, D S Choi, A Dierich

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université L. Pasteur de Strasbourg, Illkirch, France.

Proceedings of the National Academy of Sciences of the United States of America
|August 16, 2000
PubMed
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The serotonin 5-HT(2B) receptor is crucial for heart development. Its absence causes embryonic death due to heart defects, impacting cardiac differentiation and myocyte proliferation.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Pharmacology

Background:

  • Serotonin (5-hydroxytryptamine, 5-HT) is known to regulate cardiovascular functions.
  • While various 5-HT receptors exist, their specific roles in embryonic development, particularly cardiac development, remain incompletely understood.
  • Previous studies on 5-HT receptor disruptions in mice have not yielded embryonic defects.

Purpose of the Study:

  • To investigate the role of the 5-HT(2B) receptor in cardiac development.
  • To determine the consequences of 5-HT(2B) receptor gene inactivation on embryonic and neonatal heart formation.
  • To elucidate the signaling pathways involved in 5-HT(2B) receptor-mediated cardiac differentiation.

Main Methods:

  • Generation and analysis of 5-HT(2B) receptor knockout mice.

Related Experiment Videos

  • Histopathological examination of embryonic and neonatal hearts.
  • Assessment of cardiac gene expression, specifically focusing on tyrosine kinase receptors like ErbB-2.
  • Evaluation of myocyte proliferation and differentiation in mutant models.

    • Main Results:

    • Inactivation of the 5-HT(2B) receptor gene resulted in embryonic and neonatal lethality due to severe heart defects.
    • Mutant embryos displayed a lack of cardiac trabeculae and reduced expression of the tyrosine kinase receptor ErbB-2.
    • Surviving newborn mice exhibited ventricular hypoplasia, indicating impaired myocyte proliferation.
    • Adult mutant mice showed cardiac histopathology, including myocyte disarray and ventricular dilation.

    Conclusions:

    • The 5-HT(2B) receptor is a critical regulator of cardiac development, influencing both differentiation and proliferation.
    • The Gq-coupled 5-HT(2B) receptor appears to signal through the ErbB-2 tyrosine kinase pathway during cardiac differentiation.
    • This study provides a genetic model for cardiopathies, offering insights into the pathogenesis and potential therapies for human cardiac disorders.