Alcohol exposure induces chick craniofacial bone defects by negatively affecting cranial neural crest development

Ping Zhang, Guang Wang, Zhuangling Lin, Yushi Wu, Jing Zhang, Meng Liu, Kenneth Ka Ho Lee, Manli Chuai, Xuesong Yang (Lead / Corresponding author)

Research output: Contribution to journalArticle

7 Citations (Scopus)
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Abstract

Excess alcohol consumption during pregnancy could lead to fetal alcohol syndrome (FAS). However, the molecular mechanism leading to craniofacial abnormality, a feature of FAS, is still poorly understood. The cranial neural crest cells (NCCs) contribute to the formation of the craniofacial bones. Therefore, NCCs exposed to ethanol was investigated - using chick embryos and in vitro explant culture as experimental models. We demonstrated that exposure to 2% ethanol induced craniofacial defects, which includes parietal defect, in the developing chick fetus. Immunofluorescent staining revealed that ethanol treatment downregulated Ap-2ɑ, Pax7 and HNK-1 expressions by cranial NCCs. Using double-immunofluorescent stainings for Ap-2ɑ/pHIS3 and Ap-2ɑ/c-Caspase3, we showed that ethanol treatment inhibited cranial NCC proliferation and increased NCC apoptosis, respectively. Moreover, ethanol treatment of the dorsal neuroepithelium increased Laminin, N-Cadherin and Cadherin 6B expressions while Cadherin 7 expression was repressed. In situ hybridization also revealed that ethanol treatment up-regulated Cadherin 6B expression but down-regulated slug, Msx1, FoxD3 and BMP4 expressions. In summary, our experimental results demonstrated that ethanol treatment interferes with the production of cranial NCCs by affecting the proliferation and apoptosis of these cells. In addition, ethanol affected the delamination, epithelial-mesenchymal transition (EMT) and cell migration of cranial NCCs, which may have contributed to the etiology of the craniofacial defects.

Original languageEnglish
Pages (from-to)53-64
Number of pages12
JournalToxicology Letters
Volume281
Early online date14 Sep 2017
DOIs
Publication statusPublished - 5 Nov 2017

Keywords

  • Alcohol
  • Cranial neural crest cells
  • Delamination
  • Migration
  • EMT
  • Apoptosis

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