Work

Pharmacological exposures may precipitate craniosynostosis through targeted stem cell depletion

Year: 2019

Type: article

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.

Source: Stem Cell Research

DOI: 10.1016/j.scr.2019.101528

Authors: Emily Durham, R. Nicole Howie, Nicholas Larson, Amanda LaRue, James Cray

Institutions: Medical University of South Carolina, Ralph H. Johnson VA Medical Center, The Ohio State University Wexner Medical Center, The Ohio State University

Language: English

Topic: Craniofacial Disorders and Treatments

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,100