PUBLICATION

Temporal characterization of optic fissure basement membrane composition suggests nidogen may be an initial target of remodeling

Authors
Nicholas, C., Weaver, M., Piedade, W.P., Vocking, O., Famulski, J.K.
ID
ZDB-PUB-190430-8
Date
2019
Source
Developmental Biology   452(1): 43-54 (Journal)
Registered Authors
Keywords
Basement membrane, Coloboma, Extracellular matrix, Nidogen, Optic fissure, Retina
MeSH Terms
  • Animals
  • Basement Membrane/embryology*
  • Gene Expression Regulation, Developmental*
  • Membrane Glycoproteins/genetics
  • Membrane Glycoproteins/metabolism*
  • Retina/embryology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
31034836 Full text @ Dev. Biol.
Abstract
Fusion of the optic fissure is necessary to complete retinal morphogenesis and ensure proper function of the optic stalk. Failure of this event leads to congenital coloboma, one of the leading causes of pediatric blindness. Mechanistically it is widely accepted that the basement membrane (BM) surrounding the maturing retina needs to be remodeled within the fissure in order to facilitate subsequent epithelial sheet fusion. However, the mechanism driving BM remodeling has yet to be elucidated. As a first step to understanding this critical molecular event we comprehensively characterized the core composition of optic fissure BMs in the zebrafish embryos. Zebrafish optic fissure BMs were found to express laminin a1, a4, b1a, c1 and c3, nidogen 1a, 1b and 2a, collagen IV a1 and a2 as well as perlecan. Furthermore, we observed that laminin, perlecan and collagen IV expression persists in the fissure during fusion, up to 56 hpf, while nidogen expression is downregulated upon initiation of fusion, at 36 hpf. Using immunohistochemistry we also show that nidogen is removed from the BM prior to that of laminin, indicating that remodeling of the BM is an ordered event. Lastly, we characterized retinal morphogenesis in the absence of nidogen function and documented retinal malformation similar to what is observed in laminin mutants. Taken together, we propose a model of BM remodeling where nidogen acts as a linchpin during initiation of optic fissure fusion.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes