Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion
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 embryoni...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/43877 |
| _version_ | 1811181468939976704 |
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| author | Holly Hardy James GD Prendergast Aara Patel Sunit Dutta Violeta Trejo-Reveles Hannah Kroeger Andrea R Yung Lisa V Goodrich Brian Brooks Jane C Sowden Joe Rainger |
| author_facet | Holly Hardy James GD Prendergast Aara Patel Sunit Dutta Violeta Trejo-Reveles Hannah Kroeger Andrea R Yung Lisa V Goodrich Brian Brooks Jane C Sowden Joe Rainger |
| author_sort | Holly Hardy |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:18:15Z |
| format | Article |
| id | doaj.art-954b152a5b0d453aa0310ee5b9f00758 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:15Z |
| publishDate | 2019-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-954b152a5b0d453aa0310ee5b9f007582022-12-22T04:32:17ZengeLife Sciences Publications LtdeLife2050-084X2019-06-01810.7554/eLife.43877Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusionHolly Hardy0https://orcid.org/0000-0003-4603-7784James GD Prendergast1https://orcid.org/0000-0001-8916-018XAara Patel2Sunit Dutta3Violeta Trejo-Reveles4Hannah Kroeger5Andrea R Yung6https://orcid.org/0000-0002-4053-378XLisa V Goodrich7Brian Brooks8Jane C Sowden9Joe Rainger10https://orcid.org/0000-0003-1091-5100The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United KingdomThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United KingdomBirth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United KingdomOphthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, United StatesThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United KingdomThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United KingdomDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesOphthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, United StatesBirth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United KingdomThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United KingdomEpithelial 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.https://elifesciences.org/articles/43877optic fissure closureepithelial fusionnetrincolobomacleft palateCHARGE syndrome |
| spellingShingle | Holly Hardy James GD Prendergast Aara Patel Sunit Dutta Violeta Trejo-Reveles Hannah Kroeger Andrea R Yung Lisa V Goodrich Brian Brooks Jane C Sowden Joe Rainger Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion eLife optic fissure closure epithelial fusion netrin coloboma cleft palate CHARGE syndrome |
| title | Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion |
| title_full | Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion |
| title_fullStr | Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion |
| title_full_unstemmed | Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion |
| title_short | Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion |
| title_sort | detailed analysis of chick optic fissure closure reveals netrin 1 as an essential mediator of epithelial fusion |
| topic | optic fissure closure epithelial fusion netrin coloboma cleft palate CHARGE syndrome |
| url | https://elifesciences.org/articles/43877 |
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