Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina
| Autor: | Nicole M. Duff, Lucia Caceres, Keon Collett, Elizabeth A. Cairns, Christopher R. McMaster, Johane M Robitaille, Gheyath K. Nasrallah, Mike Ngo, Sergey V. Prykhozhij, Harald Gjerde, Matthew K. Litvak, Jason N. Berman |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Frizzled Embryo Nonmammalian FZD4 Familial Exudative Vitreoretinopathies Vascular Remodeling optokinetic response pericytes Retina Animals Genetically Modified 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Retinal Diseases medicine Animals Humans Zebrafish Body Patterning biology Neovascularization Pathologic Retinal Vessels Retinal Zebrafish Proteins medicine.disease biology.organism_classification Frizzled Receptors Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry FEVR Retinal vasculature Familial exudative vitreoretinopathy Feasibility Studies Blood vessel remodeling 030217 neurology & neurosurgery Developmental Biology Blood vessel |
| Zdroj: | Developmental dynamics : an official publication of the American Association of AnatomistsREFERENCES. 248(12) |
| ISSN: | 1097-0177 |
| Popis: | Familial exudative vitreoretinopathy (FEVR) is a rare congenital disorder characterized by a lack of blood vessel growth to the periphery of the retina with secondary fibrovascular proliferation at the vascular-avascular junction. These structurally abnormal vessels cause leakage and hemorrhage, while the fibroproliferative scarring results in retinal dragging, detachment and blindness. Mutations in the FZD4 gene represent one of the most common causes of FEVR. A loss of function mutation resulting from a 10-nucleotide insertion into exon 1 of the zebrafish fzd4 gene was generated using transcription activator-like effector nucleases (TALENs). Structural and functional integrity of the retinal vasculature was examined by fluorescent microscopy and optokinetic responses. Zebrafish retinal vasculature is asymmetrically distributed along the dorsoventral axis, with active vascular remodeling on the ventral surface of the retina throughout development. fzd4 mutants exhibit disorganized ventral retinal vasculature with discernable tubular fusion by week 8 of development. Furthermore, fzd4 mutants have impaired optokinetic responses requiring increased illumination. We have generated a visually impaired zebrafish FEVR model exhibiting abnormal retinal vasculature. These fish provide a tractable system for studying vascular biology in retinovascular disorders, and demonstrate the feasibility of using zebrafish for evaluating future FEVR genes identified in humans. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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