Pharmacological exposures may precipitate craniosynostosis through targeted stem cell depletion.

Abstract

The Centers for Disease Control and Prevention, National Birth Defects Study suggests that environmental exposures including maternal thyroid diseases, maternal nicotine use, and use of selective serotonin reuptake inhibitors (SSRIs) may exacerbate incidence and or severity of craniofacial abnormalities including craniosynostosis. Premature fusion of a suture(s) of the skull defines the birth defect craniosynostosis which occurs in 1:1800-2500 births. A proposed mechanism of craniosynostosis is the disruption of proliferation and differentiation of cells in the perisutural area. Here, we hypothesize that pharmacological exposures including excess thyroid hormone, nicotine, and SSRIs lead to an alteration of stem cells within the sutures resulting in premature fusion. In utero exposure to nicotine and citalopram (SSRI) increased the risk of premature suture fusion in a wild-type murine model. Gli1+ stem cells were reduced, stem cell populations were depleted, and homeostasis of the suture mesenchyme was altered with exposure. Thus, although these pharmacological exposures can deplete calvarial stem cell populations leading to craniosynostosis, depletion of stem cells is not a unifying mechanism for pharmacological exposure associated craniosynostosis.

• Authors: Emily Durham, R Nicole Howie, Nicholas Larson, Amanda LaRue, James Cray
• Journal: Stem cell research (Stem Cell Res) Vol. 40 Pg. 101528 (10 2019) ISSN: 1876-7753 [Electronic] England
• PMID: 31415959 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Culture Media
• Serotonin Uptake Inhibitors
• Thyroid Hormones
• Zinc Finger Protein GLI1
• Citalopram
• Nicotine
• Thyroxine

Topics

• Animals
• Citalopram (pharmacology)
• Craniosynostoses (etiology)
• Culture Media (chemistry)
• Down-Regulation (drug effects)
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Nicotine (pharmacology)
• Selective Serotonin Reuptake Inhibitors (pharmacology)
• Skull (anatomy & histology, diagnostic imaging, growth & development)
• Stem Cells (drug effects, metabolism, pathology)
• Thyroid Hormones (pharmacology)
• Thyroxine (pharmacology)
• Zinc Finger Protein GLI1 (genetics, metabolism)