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

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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

Fingerprint

Neural Crest
Bone
Ethanol
Alcohols
Bone and Bones
Defects
Cadherins
Fetal Alcohol Spectrum Disorders
Craniofacial Abnormalities
Cell Proliferation
Apoptosis
Staining and Labeling
Gastropoda
Epithelial-Mesenchymal Transition
Cell proliferation
Laminin
Chick Embryo
Delamination
Osteogenesis
Alcohol Drinking

Keywords

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

Cite this

Zhang, Ping ; Wang, Guang ; Lin, Zhuangling ; Wu, Yushi ; Zhang, Jing ; Liu, Meng ; Lee, Kenneth Ka Ho ; Chuai, Manli ; Yang, Xuesong. / Alcohol exposure induces chick craniofacial bone defects by negatively affecting cranial neural crest development. In: Toxicology Letters. 2017 ; Vol. 281. pp. 53-64.
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title = "Alcohol exposure induces chick craniofacial bone defects by negatively affecting cranial neural crest development",
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.",
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author = "Ping Zhang and Guang Wang and Zhuangling Lin and Yushi Wu and Jing Zhang and Meng Liu and Lee, {Kenneth Ka Ho} and Manli Chuai and Xuesong Yang",
note = "This work was supported by National Natural Science Foundation of China (31771331, 81571436, 31401230), Science and Technology Planning Project of Guangdong Province (2017A050506029, 2016B030229002, 2014A020213008, 2014A020221091), Science and Technology Program of Guangzhou (201710010054, 201510010073), Guangdong Natural Science Foundation (2016A030311044), The Fundamental Research Funds for the Central Universities (21617466) and Research Grant of Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University (ZSYX-M-00001 & ZSYX-T-00001) to Dr. Wang G and Yang X.",
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Alcohol exposure induces chick craniofacial bone defects by negatively affecting cranial neural crest development. / Zhang, Ping; Wang, Guang; Lin, Zhuangling; Wu, Yushi; Zhang, Jing; Liu, Meng; Lee, Kenneth Ka Ho; Chuai, Manli; Yang, Xuesong (Lead / Corresponding author).

In: Toxicology Letters, Vol. 281, 05.11.2017, p. 53-64.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alcohol exposure induces chick craniofacial bone defects by negatively affecting cranial neural crest development

AU - Zhang, Ping

AU - Wang, Guang

AU - Lin, Zhuangling

AU - Wu, Yushi

AU - Zhang, Jing

AU - Liu, Meng

AU - Lee, Kenneth Ka Ho

AU - Chuai, Manli

AU - Yang, Xuesong

N1 - This work was supported by National Natural Science Foundation of China (31771331, 81571436, 31401230), Science and Technology Planning Project of Guangdong Province (2017A050506029, 2016B030229002, 2014A020213008, 2014A020221091), Science and Technology Program of Guangzhou (201710010054, 201510010073), Guangdong Natural Science Foundation (2016A030311044), The Fundamental Research Funds for the Central Universities (21617466) and Research Grant of Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University (ZSYX-M-00001 & ZSYX-T-00001) to Dr. Wang G and Yang X.

PY - 2017/11/5

Y1 - 2017/11/5

N2 - 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.

AB - 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.

KW - Alcohol

KW - Cranial neural crest cells

KW - Delamination

KW - Migration

KW - EMT

KW - Apoptosis

U2 - 10.1016/j.toxlet.2017.09.010

DO - 10.1016/j.toxlet.2017.09.010

M3 - Article

C2 - 28919490

VL - 281

SP - 53

EP - 64

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -