Document Type
Article
Publication Date
7-2025
Abstract
Background: Cardiac neural crest cells (cNCCs) are critical for heart development, and their disruption can result in congenital heart defects. Serotonin (5-HT) signaling, specifically via 5-HT2B and 5-HT2C receptors, regulates diverse physiological processes, including neural crest migration. This study investigates how modulation of 5-HT2B and 5-HT2C receptor activity impacts cNCC migration and the development of their derivatives, with relevance to serotonergic drug safety during pregnancy.
Methods
Chicken embryos at HH8 were treated with 50 μL of 20 μM 1-Methylpsilocin (1-MP), an inverse agonist of 5-HT2B and agonist of 5-HT2C, and collected at HH14 to assess cNCC migration. Embryos were pre-treated with SB242084, a selective 5-HT2C antagonist, to isolate receptor-specific contributions before 1-MP application. Phenotypic outcomes were assessed at HH32 and HH36 for structural heart defects.
Results
1-MP disrupted cNCC migration at HH14, evidenced by abnormal shortening of the circumpharyngeal neural crest (CirNCC) stream. Pre-treatment with SB242084 did not rescue the phenotype, implicating 5-HT2B as the primary driver, though potential contributions from 5-HT2C cannot be excluded. At HH32, 1-MP-treated embryos displayed gaps in the aorticopulmonary septum. By HH36, interventricular septal defects and delayed development further supported the role of 5-HT2B in cNCC migration and differentiation.
Conclusion
These findings reveal that 5-HT2B receptor activity is critical for cNCC migration and heart development. They underscore the potential teratogenic risks of serotonergic drugs targeting 5-HT2B/5-HT2C receptors during pregnancy, with implications for drug safety and heart morphogenesis.
Original Publication Citation
Wells, B. K., Garramone, G. K., Mahomed, A., & Ezin, M. (2025). Teratogenic Effects of Serotonin Receptor 2B Disruption on the Migration and Cardiac Derivatives of the Cardiac Neural Crest. Birth Defects Research, 117(7), e2506. https://doi.org/10.1002/bdr2.2506
Publisher Statement
© 2025 The Author(s). Birth Defects Research published by Wiley Periodicals LLC.
Digital Commons @ LMU & LLS Citation
Wells, Brian K.; Garramone, Gwyneth K.; Mahomed, Amira; and Ezin, Max, "Teratogenic Effects of Serotonin Receptor 2B Disruption on the Migration and Cardiac Derivatives of the Cardiac Neural Crest" (2025). Biology Faculty Works. 225.
https://digitalcommons.lmu.edu/bio_fac/225
