ZFIN ID: ZDB-PUB-200423-1
In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP
Eckert, P., Knickmeyer, M.D., Heermann, S.
Date: 2020
Source: International Journal of Molecular Sciences   21(8): (Journal)
Registered Authors: Heermann, Stephan
Keywords: BMP, POM, basal lamina, hyaloid vessel, optic fissure, pioneer cells
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/metabolism
  • Basement Membrane/metabolism
  • Blood Vessels/anatomy & histology
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism*
  • Coloboma/metabolism
  • Coloboma/pathology
  • Optic Disk/abnormalities
  • Retinal Pigment Epithelium/cytology
  • Retinal Pigment Epithelium/metabolism
  • Time-Lapse Imaging
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 32316164 Full text @ Int. J. Mol. Sci.
Colobomata, persistent optic fissures, frequently cause congenital blindness. Here, we focused on optic fissure fusion using in vivo time-lapse imaging in zebrafish. We identified the fusion initiating cells, which we termed "pioneer cells." Based on morphology, localization, and downregulation of the neuroretinal (NR) precursor marker rx2, these cells could be considered as retinal pigment epithelial (RPE) progenitors. Notably, pioneer cells regain rx2 expression and integrate into the NR after fusion, indicating that they do not belong to the pool of RPE progenitors, supported by the lack of RPE marker expression in pioneer cells. They establish the first cellular contact between the margins in the proximal fissure region and separate the hyaloid artery and vein. After initiation, the fusion site is progressing distally, increasing the distance between the hyaloid artery and vein. A timed BMP (Bone Morphogenetic Protein) induction, resulting in coloboma, did not alter the morphology of the fissure margins, but it did affect the expression of NR and RPE markers within the margins. In addition, it resulted in a persisting basal lamina and persisting remnants of periocular mesenchyme and hyaloid vasculature within the fissure, supporting the necessity of BMP antagonism within the fissure margins. The hampered fissure fusion had severe effects on the vasculature of the eye.