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Chem Biol. 2014 Apr 24;21(4):488-501. doi: 10.1016/j.chembiol.2014.02.013. Epub 2014 Mar 27.

Neural crest development and craniofacial morphogenesis is coordinated by nitric oxide and histone acetylation.

Author information

1
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Shriners Hospitals for Children, Boston, MA 02114, USA.
2
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
3
Howard Hughes Medical Institute, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
4
Howard Hughes Medical Institute, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA.
5
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Shriners Hospitals for Children, Boston, MA 02114, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA. Electronic address: cliao@partners.org.

Abstract

Cranial neural crest (CNC) cells are patterned and coalesce to facial prominences that undergo convergence and extension to generate the craniofacial form. We applied a chemical genetics approach to identify pathways that regulate craniofacial development during embryogenesis. Treatment with the nitric oxide synthase inhibitor 1-(2-[trifluoromethyl] phenyl) imidazole (TRIM) abrogated first pharyngeal arch structures and induced ectopic ceratobranchial formation. TRIM promoted a progenitor CNC fate and inhibited chondrogenic differentiation, which were mediated through impaired nitric oxide (NO) production without appreciable effect on global protein S-nitrosylation. Instead, TRIM perturbed hox gene patterning and caused histone hypoacetylation. Rescue of TRIM phenotype was achieved with overexpression of histone acetyltransferase kat6a, inhibition of histone deacetylase, and complementary NO. These studies demonstrate that NO signaling and histone acetylation are coordinated mechanisms that regulate CNC patterning, differentiation, and convergence during craniofacial morphogenesis.

PMID:
24684905
PMCID:
PMC4349424
DOI:
10.1016/j.chembiol.2014.02.013
[Indexed for MEDLINE]
Free PMC Article

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