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

Autor:	Hardy H; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom., Prendergast JG; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom., Patel A; Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom., Dutta S; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, United States., Trejo-Reveles V; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom., Kroeger H; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom., Yung AR; Department of Neurobiology, Harvard Medical School, Boston, United States., Goodrich LV; Department of Neurobiology, Harvard Medical School, Boston, United States., Brooks B; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, United States., Sowden JC; Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom., Rainger J; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2019 Jun 04; Vol. 8. Date of Electronic Publication: 2019 Jun 04.
DOI:	10.7554/eLife.43877
Abstrakt:	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. Competing Interests: HH, JP, AP, SD, VT, HK, AY, LG, BB, JS, JR No competing interests declared (© 2019, Hardy et al.)
Databáze:	MEDLINE
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