Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion: .

Holly Hardy, James Prendergast, A. Patel, S. Dutta , Violeta Trejo-Reveles, Hannah Kroeger, A. Yung , L. Goodrich , B. P. Brooks , J. Sowden , Jonathan Rainger

Research output: Contribution to journalArticlepeer-review

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
Original languageEnglish
Article numbere43877
Pages (from-to)1-23
JournaleLIFE
Volume8
Early online date4 Jun 2019
DOIs
Publication statusE-pub ahead of print - 4 Jun 2019

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