Hardy, H;
Prendergast, JGD;
Patel, A;
Dutta, S;
Trejo-Reveles, V;
Kroeger, H;
Yung, AR;
... Rainger, J; + view all
(2019)
Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion.
eLife
, 8
, Article e43877. 10.7554/eLife.43877.
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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 during fusion 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.
| Type: | Article |
|---|---|
| Title: | Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.43877 |
| Publisher version: | https://doi.org/10.7554/eLife.43877 |
| Language: | English |
| Additional information: | Copyright © 2019, Hardy et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10082348 |
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