PUBLICATION
Hyaloid vasculature and mmp2 activity play a role during optic fissure fusion in zebrafish
- Authors
- Weaver, M.L., Piedade, W.P., Meshram, N.N., Famulski, J.K.
- ID
- ZDB-PUB-200625-2
- Date
- 2020
- Source
- Scientific Reports 10: 10136 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Basement Membrane/metabolism
- Coloboma/etiology
- Embryo, Nonmammalian*
- Eye/blood supply*
- Eye/embryology*
- Gene Expression
- Gene Expression Regulation, Developmental/genetics*
- Matrix Metalloproteinase 2/genetics*
- Matrix Metalloproteinase 2/metabolism
- Matrix Metalloproteinase 2/physiology*
- Morphogenesis/genetics*
- Mutation
- PAX2 Transcription Factor/genetics
- PAX2 Transcription Factor/physiology
- Retina/embryology*
- Zebrafish/embryology*
- Zebrafish/genetics*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology
- PubMed
- 32576859 Full text @ Sci. Rep.
Citation
Weaver, M.L., Piedade, W.P., Meshram, N.N., Famulski, J.K. (2020) Hyaloid vasculature and mmp2 activity play a role during optic fissure fusion in zebrafish. Scientific Reports. 10:10136.
Abstract
Vertebrate retinal development requires timely and precise fusion of the optic fissure (OF). Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed OF fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a-/- embryos fail to accumulate F-actin in the OF prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a-/- embryos. When examining the connection between pax2a loss of function and hyaloid vasculature, we observed significant reduction of talin1 expression, a regulator of hyaloid vasculature. In addition, cranial VEGF expression was found to be reduced in pax2a-/- embryos. Pharmacological inhibition of VEGF signaling phenocopied the pax2a-/- vasculature, F-actin and BM degradation phenotypes. Lastly, we determined that OF associated hyaloid vasculature is a source of mmp2, mmp14a and mmp14b expression and showed that mmp2 is functionally necessary for degradation of OF BM. Taken together we propose a pax2a driven mechanism that ensures proper and timely hyaloid vasculature invasion of the OF in order to facilitate availability of the BM remodeler mmp2.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping