Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina

Caceres, L., Prykhozhij, S.V., Cairns, E., Gjerde, H., Duff, N.M., Collett, K., Ngo, M., Nasrallah, G.K., McMaster, C.R., Litvak, M., Robitaille, J.M., Berman, J.N.
Developmental Dynamics : an official publication of the American Association of Anatomists   248(12): 1243-1256 (Journal)
Registered Authors
Berman, Jason, Caceres, Lucia, Nasrallah, Gheyath, Prykhozhij, Sergey
FEVR, Retinal vasculature, optokinetic response, pericytes
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/genetics
  • Disease Models, Animal
  • Embryo, Nonmammalian
  • Familial Exudative Vitreoretinopathies/diagnosis
  • Familial Exudative Vitreoretinopathies/genetics
  • Familial Exudative Vitreoretinopathies/pathology
  • Feasibility Studies
  • Frizzled Receptors/physiology
  • Humans
  • Neovascularization, Pathologic/embryology
  • Neovascularization, Pathologic/genetics
  • Neovascularization, Pathologic/physiopathology
  • Retina/diagnostic imaging
  • Retina/embryology
  • Retina/metabolism
  • Retina/pathology*
  • Retinal Diseases/genetics
  • Retinal Diseases/pathology
  • Retinal Vessels/embryology
  • Retinal Vessels/pathology*
  • Retinal Vessels/physiology
  • Vascular Remodeling/genetics*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/physiology
31566834 Full text @ Dev. Dyn.
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.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes