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

Nicholas Carrara, Megan Weaver, Warlen Pereira Piedade, Oliver Vöcking, J. K. Famulski

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish
Pages (from-to)43-54
Number of pages12
JournalDevelopmental Biology
Issue number1
StatePublished - Aug 1 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.


  • Basement membrane
  • Coloboma
  • Extracellular matrix
  • Nidogen
  • Optic fissure
  • Retina

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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