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ABSTRACT Neural crest cells (NCCs) are a dynamic, multipotent, vertebrate-specific population of embryonic stem cells. These ectodermally-derived cells contribute to diverse tissue types in developing embryos including craniofacial bone and cartilage, the peripheral and enteric nervous systems and pigment cells, among a host of other cell types. Due to their contribution to a significant number of adult tissue types, the mechanisms that drive their formation, migration and differentiation are highly studied. NCCs have a unique ability to transition from tightly adherent epithelial cells to mesenchymal and migratory cells by altering their polarity, expression of cell-cell adhesion molecules and gaining invasive abilities. In this Review, we discuss classical and emerging factors driving NCC epithelial-to-mesenchymal transition and migration, highlighting the role of signaling and transcription factors, as well as novel modifying factors including chromatin remodelers, small RNAs and post-translational regulators, which control the availability and longevity of major NCC players.
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This content will become publicly available on May 1, 2026
NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos
Embryonic exposures to non-steroidal anti-inflammatory drugs (NSAIDs) have been linked to preterm birth, neural tube closure defects, abnormal enteric innervation, and craniofacial malformations, potentially due to disrupted neural tube or neural crest (NC) cell development. Naproxen (NPX), a common non-steroidal anti-inflammatory drug (NSAID) used to relieve pain and inflammation, exerts its effects through non-selective cyclooxygenase (COX) inhibition. Our lab has identified that the cyclooxygenase (COX-1 and COX-2) isoenzymes are expressed during the early stages of vertebrate embryonic development, and that global inhibition of COX-1 and COX-2 function disrupts NC cell migration and differentiation in Ambystoma mexicanum (axolotl) embryos. NC cells differentiate into various adult tissues including craniofacial cartilage, bone, and neurons in the peripheral and enteric nervous systems. To investigate the specific phenotypic and molecular effects of NPX exposure on NC development and differentiation, and to identify molecular links between COX inhibition and NC derivative anomalies, we exposed late neurula and early tailbud stage axolotl embryos to various concentrations of NPX and performed immunohistochemistry (IHC) for markers of migratory and differentiating NC cells. Our results reveal that NPX exposure impairs the migration of SOX9+ NC cells, leading to abnormal development of craniofacial cartilage structures, including Meckel's cartilage in the jaw. NPX exposure also alters the expression of markers associated with peripheral and central nervous system (PNS and CNS) development, suggesting concurrent neurodevelopmental changes.
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- Award ID(s):
- 2143217
- PAR ID:
- 10657093
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Differentiation
- Volume:
- 143
- Issue:
- C
- ISSN:
- 0301-4681
- Page Range / eLocation ID:
- 100856
- Subject(s) / Keyword(s):
- Cyclooxygenase, COX-1, COX-2, Neural crest, Axolotl, Naproxen, NSAID
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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