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

Yawei Kong, Michael Grimaldi, Eugene Curtin, Max Dougherty, Charles Kaufman, Richard M. White, Leonard I. Zon, Eric C. Liao

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish
Pages (from-to)488-501
Number of pages14
JournalChemistry and Biology
Volume21
Issue number4
DOIs
StatePublished - Apr 24 2014

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