PUBLICATION
Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion
- Authors
- Hardy, H., Prendergast, J.G., Patel, A., Dutta, S., Trejo-Reveles, V., Kroeger, H., Yung, A.R., Goodrich, L.V., Brooks, B., Sowden, J.C., Rainger, J.
- ID
- ZDB-PUB-190605-12
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Brooks, Brian P., Dutta, Sunit
- Keywords
- chicken, developmental biology, human, human biology, medicine, mouse, zebrafish
- MeSH Terms
-
- Chick Embryo
- Netrin-1/genetics*
- Animals
- Epithelial Cells/metabolism
- Humans
- Gene Expression Profiling
- Apoptosis/genetics
- Coloboma/genetics*
- Coloboma/pathology
- Eye/growth & development*
- Eye/pathology
- Mice
- Gene Expression Regulation, Developmental/genetics
- Zebrafish/genetics
- Zebrafish/growth & development
- Conserved Sequence/genetics
- Evolution, Molecular*
- Palate/growth & development
- Palate/pathology
- Chickens
- PubMed
- 31162046 Full text @ Elife
Citation
Hardy, H., Prendergast, J.G., Patel, A., Dutta, S., Trejo-Reveles, V., Kroeger, H., Yung, A.R., Goodrich, L.V., Brooks, B., Sowden, J.C., Rainger, J. (2019) Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion. eLIFE. 8:.
Abstract
Epithelial fusion underlies many vital organogenic processes during embryogenesis. Disruptions to these cause a significant number of human birth defects, including ocular coloboma. We provide robust spatial-temporal staging and unique anatomical detail of optic fissure closure (OFC) in the embryonic chick, including evidence for roles of apoptosis and epithelial remodelling. We performed complementary transcriptomic profiling and show that Netrin-1 (NTN1) is precisely expressed in the chick fissure margin at the fusion plate but is immediately downregulated after fusion. We further provide a combination of protein localisation and phenotypic evidence in chick, humans, mice and zebrafish that Netrin-1 has an evolutionarily conserved and essential requirement for OFC, and is likely to have an important role in palate fusion. Our data suggest that NTN1 is a strong candidate locus for human coloboma and other multi-system developmental fusion defects, and show that chick OFC is a powerful model for epithelial fusion research.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping