PUBLICATION
In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP
- Authors
- Eckert, P., Knickmeyer, M.D., Heermann, S.
- ID
- ZDB-PUB-200423-1
- 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.
Citation
Eckert, P., Knickmeyer, M.D., Heermann, S. (2020) In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP. International Journal of Molecular Sciences. 21(8):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping