title: The hyaloid vasculature facilitates basement membrane breakdown during choroid fissure closure in the zebrafish eye.
abstract: A critical aspect of vertebrate eye development is closure of the choroid fissure (CF). Defects in CF closure result in colobomas, which are a significant cause of childhood blindness worldwide. Despite the growing number of mutated loci associated with colobomas, we have a limited understanding of the cell biological underpinnings of CF closure. Here, we utilize the zebrafish embryo to identify key phases of CF closure and regulators of the process. Utilizing Laminin-111 as a marker for the basement membrane (BM) lining the CF, we determine the spatial and temporal patterns of BM breakdown in the CF, a prerequisite for CF closure. Similarly, utilizing a combination of in vivo time-lapse imaging, β-catenin immunohistochemistry and F-actin staining, we determine that tissue fusion, which serves to close the fissure, follows BM breakdown closely. Periocular mesenchyme (POM)-derived endothelial cells, which migrate through the CF to give rise to the hyaloid vasculature, possess distinct actin foci that correlate with regions of BM breakdown. Disruption of talin1, which encodes a regulator of the actin cytoskeleton, results in colobomas and these correlate with structural defects in the hyaloid vasculature and defects in BM breakdown. cloche mutants, which entirely lack a hyaloid vasculature, also possess defects in BM breakdown in the CF. Taken together, these data support a model in which the hyaloid vasculature and/or the POM-derived endothelial cells that give rise to the hyaloid vasculature contribute to BM breakdown during CF closure.
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin TX, 78712.|Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
authors.forename: Andrea
authors.initials: A
authors.lastname: James
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin TX, 78712.
authors.forename: Chanjae
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin TX, 78712.
authors.forename: Andre M
authors.initials: AM
authors.lastname: Williams
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin TX, 78712.|Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
authors.forename: Krista
authors.initials: K
authors.lastname: Angileri
authors.affiliation: Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.|Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA 15213.
authors.forename: Kira L
authors.initials: KL
authors.lastname: Lathrop
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin TX, 78712.|Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.|Department of Developmental Biology, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gross
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D002829:Choroid / Q000098:blood supply / Q000196:embryology* / Q000648:ultrastructure; D003103:Coloboma / Q000196:embryology / Q000235:genetics; D008648:Mesoderm / Q000502:physiology; D008845:Microinjections; D009880:Ophthalmic Artery / Q000196:embryology*; D012333:RNA, Messenger / Q000235:genetics; D016608:Talin / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012333:RNA, Messenger; D016608:Talin; D029961:Zebrafish Proteins; C000609736:npas4l protein, zebrafish; C000621875:tln1 protein, zebrafish