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Published on: September 30, 2013
Chemical-induced craniofacial anomalies caused by disruption of neural crest cell development in a zebrafish model
Shujie Liu1, Rika Narumi1, Naohiro Ikeda1
1R&D, Safety Science Research, Kao Corporation, Tochigi, Japan.
Background:
Craniofacial anomalies are among the most frequent birth defects worldwide, and are thought to be caused by gene-environment interactions. Genetically manipulated zebrafish simulate human diseases and provide great advantages for investigating the etiology and pathology of craniofacial anomalies. Although substantial advances have been made in understanding genetic factors causing craniofacial disorders, limited information about the etiology by which environmental factors, such as teratogens, induce craniofacial anomalies is available in zebrafish.
Results:
Zebrafish embryos displayed craniofacial malformations after teratogen treatments. Further observations revealed characteristic disruption of chondrocyte number, shape and stacking. These findings suggested aberrant development of cranial neural crest (CNC) cells, which was confirmed by gene expression analysis of the CNC. Notably, these observations suggested conserved etiological pathways between zebrafish and mammals including human. Furthermore, several of these chemicals caused malformations of the eyes, otic vesicle, and/or heart, representing a phenocopy of neurocristopathy, and these chemicals altered the expression levels of the responsible genes.
Conclusions:
Our results demonstrate that chemical-induced craniofacial malformation is caused by aberrant development of neural crest. This study indicates that zebrafish provide a platform for investigating contributions of environmental factors as causative agents of craniofacial anomalies and neurocristopathy.
Insights
Zebrafish embryos exposed to teratogens developed craniofacial malformations due to disrupted neural crest development. This highlights zebrafish as a model for studying environmental causes of birth defects and neurocristopathy.
Area of Science:
- Developmental biology
- Toxicology
- Genetics
Background:
- Craniofacial anomalies are common birth defects, often resulting from gene-environment interactions.
- Zebrafish are valuable models for studying craniofacial development and disease.
- The environmental etiology of craniofacial anomalies, particularly teratogen effects, is not well understood in zebrafish.
Purpose of the Study:
- To investigate the effects of teratogens on craniofacial development in zebrafish.
- To explore the underlying mechanisms of teratogen-induced craniofacial malformations.
- To establish zebrafish as a model for neurocristopathy research.
Main Methods:
- Exposure of zebrafish embryos to teratogens.
- Microscopic observation of craniofacial structures.
- Analysis of chondrocyte development and gene expression in cranial neural crest (CNC) cells.
Main Results:
- Teratogen treatment induced craniofacial malformations in zebrafish embryos.
- Aberrant chondrocyte development and CNC cell disruption were observed.
- Findings suggest conserved etiological pathways between zebrafish and mammals, with observed neurocristopathy phenotypes.
Conclusions:
- Chemical-induced craniofacial malformations stem from aberrant neural crest development.
- Zebrafish serve as a robust platform for studying environmental factors in craniofacial anomalies and neurocristopathy.
