Inhibition of Cyclooxygenase-2 Alters Craniofacial Patterning during Early Embryonic Development of Chick

Abstract

A recent study from our lab revealed that the inhibition of cyclooxygenase-2 (COX-2) exclusively reduces the level of PGE2 (Prostaglandin E2) among prostanoids and hampers the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence cranial neural crest cell (CNCC) migration was checked in chick embryos after inhibiting COX-2 activity using etoricoxib. The compromised level of cell adhesion molecules and their upstream regulators, namely CDH1 (E-cadherin), CDH2 (N-cadherin), MSX1 (Msh homeobox 1), and TGF-β (Transforming growth factor beta), observed in the etoricoxib-treated embryos indicate that COX-2, through its downstream effector PGE2, regulates the expression of these factors perhaps to aid the migration of CNCCs. The histological features and levels of FoxD3 (Forkhead box D3), as well as PCNA (Proliferating cell nuclear antigen), further consolidate the role of COX-2 in the migration and survival of CNCCs in developing embryos. The results of the current study indicate that COX-2 plays a pivotal role in orchestrating craniofacial structures perhaps by modulating CNCC proliferation and migration during the embryonic development of chicks.

Time to go: neural crest cell epithelial-to-mesenchymal transition

“…For example, induced inflammation reduces NCC EMT and causes craniofacial defects in chick ( Li et al, 2022 ). However, embryonic exposure to non-steroidal anti-inflammatories in zebrafish, mouse and chick causes abnormal cranial and vagal NCC formation and migration, leading to craniofacial and enteric defects ( Parmar et al, 2021 ; Schill et al, 2016 ). These works suggest that there are additional understudied and less common pathways that may intersect with the more common NCC GRN pathways, such as Wnt, BMP or FGF pathways.…”

Advances in Understanding the Pathogenesis of Craniofacial Birth Defects

“…The anterior portion of the calvarium is derived from the cranial neural crest, whereas the posterior portion derives from paraxial mesoderm. In this Special Issue, Parmar et al [ 4 ] studied the role of cyclooxygenase-2 (Cox2) in calvarial development; Cox2 catalyzes the formation of prostaglandin E2 (PGE2) which is required for cell proliferation, migration, epithelial-mesenchymal transition, and differentiation in a variety of tissues. They found that loss of Cox2 leads to abnormal calvarial development.…”