Serotonin 2B receptor is required for heart development

Canan G. Nebigil, Doo Sup Choi, Andrée Dierich, Pierre Hickel, Marianne Le Meur, Nadia Messaddeq, Jean Marie Launay, Luc Maroteaux

Research output: Contribution to journalArticle

211 Scopus citations

Abstract

Several lines of evidence suggest that the serotonin (5-hydroxy-tryptamine, 5-HT) regulates cardiovascular functions during embryogenesis and adulthood. 5-HT binds to numerous cognate receptors to initiate its biological effects. However, none of the 5-HT receptor disruptions in mice have yet resulted in embryonic defects. Here we show that 5-HT(2B) receptor is an important regulator of cardiac development. We found that inactivation of 5-HT(2B) gene leads to embryonic and neonatal death caused by heart defects. 5-HT(2B) mutant embryos exhibit a lack of trabeculae in the heart and a specific reduction in the expression levels of a tyrosine kinase receptor, ErbB-2, leading to midgestation lethality. These in vivo data suggest that the Gq-coupled receptor 5-HT(2B) uses the signaling pathway of tyrosine kinase receptor ErbB-2 for cardiac differentiation. All surviving newborn mice display a severe ventricular hypoplasia caused by impaired proliferative capacity of myocytes. In adult mutant mice, cardiac histopathological changes including myocyte disarray and ventricular dilation were consistently observed. Our results constitute genetic evidence that 5-HT via 5-HT(2B) receptor regulates differentiation and proliferation of developing and adult heart. This mutation provides a genetic model for cardiopathy and should facilitate studies of both the pathogenesis and therapy of cardiac disorders in humans.

Original languageEnglish (US)
Pages (from-to)9508-9513
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number17
DOIs
StatePublished - Aug 15 2000

Keywords

  • Knockout
  • Neuregulin
  • Proliferation
  • Transactivation

ASJC Scopus subject areas

  • General

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  • Cite this

    Nebigil, C. G., Choi, D. S., Dierich, A., Hickel, P., Le Meur, M., Messaddeq, N., Launay, J. M., & Maroteaux, L. (2000). Serotonin 2B receptor is required for heart development. Proceedings of the National Academy of Sciences of the United States of America, 97(17), 9508-9513. https://doi.org/10.1073/pnas.97.17.9508