TY - JOUR
T1 - Neural crest development and craniofacial morphogenesis is coordinated by nitric oxide and histone acetylation
AU - Kong, Yawei
AU - Grimaldi, Michael
AU - Curtin, Eugene
AU - Dougherty, Max
AU - Kaufman, Charles
AU - White, Richard M.
AU - Zon, Leonard I.
AU - Liao, Eric C.
N1 - Funding Information:
We are grateful to Hazel Sive (MIT, Whitehead Institute) for helpful discussions, sharing of unpublished data, and encouragement; Jenna Galloway (Massachusetts General Hospital) for her detailed review of the manuscript; and Renee Ethier for excellent management of our aquatics facility. We thank Lei Zhong, Jinzhong Qin, and Chiachi Sun for their helpful technical assistance. This work was funded by grants to E.C.L. from the March of Dimes Basil O’Connor Award, Plastic Surgery Foundation, American Surgical Association, and Shriners Hospitals for Children. Y.K. was funded by Shriners Hospitals for Children Research Fellowship Award. L.I.Z. was supported by HHMI and NIH/NCI R01 CA103846. L.I.Z. is a founder and stockholder of Fate, Inc., a founder and stockholder of Scholar Rock, and a scientific advisor for Stemgent.
PY - 2014/4/24
Y1 - 2014/4/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84899656769&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2014.02.013
DO - 10.1016/j.chembiol.2014.02.013
M3 - Article
C2 - 24684905
AN - SCOPUS:84899656769
SN - 1074-5521
VL - 21
SP - 488
EP - 501
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 4
ER -