Department of Medicine, Division of Cardiovascular Medicine
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Developmental Biology
BACKGROUND: Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown.
RESULTS: The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch.
CONCLUSIONS: Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches via repression of cyclin-dependent kinase inhibitors. This article is protected by copyright. All rights reserved.
Histone Deacetylase, Neural Crest, Pharyngeal Arch, Craniofacial morphogenesis
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This is the Accepted Author Manuscript which will be published in final form at http://doi.org/10.1002/dvdy.24563. Accepted manuscript posted after 12 months as allowed by the publisher's author rights policy at https://authorservices.wiley.com/author-resources/Journal-Authors/licensing-open-access/open-access/self-archiving.html. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
DOI of Published Version
Milstone, Z. J., Lawson, G. and Trivedi, C. M. (2017), Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development and craniofacial morphogenesis. Dev. Dyn. doi:10.1002/dvdy.24563, http://doi.org/10.1002/dvdy.24563.
Developmental dynamics : an official publication of the American Association of Anatomists
Milstone ZJ, Lawson G, Trivedi CM. (2017). Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development and craniofacial morphogenesis.. GSBS Student Publications. https://doi.org/10.1002/dvdy.24563. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/2002