PUBLICATION
Sema3E is required for migration of cranial neural crest cells in zebrafish: Implications for the pathogenesis of CHARGE syndrome
- Authors
- Liu, Z.Z., Guo, J., Lu, Y., Liu, W., Fu, X., Yao, T., Zhou, Y., Xu, H.A.
- ID
- ZDB-PUB-190830-17
- Date
- 2019
- Source
- International journal of experimental pathology 100(4): 234-243 (Journal)
- Registered Authors
- Xu, Hong
- Keywords
- CHARGE syndrome, Chd7, cranial neural crest cells, migration, semaphorin 3E
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- CHARGE Syndrome/genetics*
- CHARGE Syndrome/metabolism*
- CHARGE Syndrome/pathology
- Cell Movement*
- DNA Helicases/genetics*
- DNA Helicases/metabolism*
- Gene Knockdown Techniques
- Humans
- Models, Animal
- Neural Crest
- Semaphorins/genetics*
- Semaphorins/metabolism*
- Zebrafish/embryology
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- PubMed
- 31464029 Full text @ Int. J. Exp. Pathol.
Citation
Liu, Z.Z., Guo, J., Lu, Y., Liu, W., Fu, X., Yao, T., Zhou, Y., Xu, H.A. (2019) Sema3E is required for migration of cranial neural crest cells in zebrafish: Implications for the pathogenesis of CHARGE syndrome. International journal of experimental pathology. 100(4):234-243.
Abstract
CHARGE syndrome is a congenital disorder with multiple malformations in the craniofacial structures, and cardiovascular and genital systems, which are mainly affected by neural crest defects caused by loss-of-function mutations within chromodomain helicase DNA-binding protein 7 (CHD7). However, many patients with CHARGE syndrome test negative for CHD7. Semaphorin 3E (sema3E) is a gene reported to be mutated in patients with CHARGE syndrome. However, its role in the pathogenesis of CHARGE syndrome has not been verified experimentally. Here, we report that the knockdown of sema3E results in severe craniofacial malformations, including small eyes, defective cartilage and an abnormal number of otoliths in zebrafish embryos, which resemble the major features of CHARGE syndrome. Further analysis reveals that the migratory cranial neural crest cells are scattered in the region of the hindbrain, and the postmigratory neural crest cells are reduced in the pharyngeal arches upon sema3E knockdown. Notably, immunostaining and time-lapse imaging analyses of a neural crest cell-labelled transgenic fish line, sox10:EGFP, show that the migration of cranial neural crest cells is severely impaired, and many of these cells are misrouted upon sema3E knockdown. Furthermore, the sox10-expressing cranial neural crest cells are scattered in chd7 homozygous mutants, which phenocopied the phenotype in sema3E morphants. Overexpression of sema3E rescues the phenotype of scattered cranial neural crest cells in chd7 homozygotes, indicating that chd7 may control the expression of sema3E to regulate cranial neural crest cell migration. Collectively, our data demonstrate that sema3E is involved in the pathogenesis of CHARGE syndrome by modulating cranial neural crest cell migration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping