Hyaloid vasculature and mmp2 activity play a role during optic fissure fusion in zebrafish
| Autor: | Jakub K. Famulski, Megan Weaver, Warlen Pereira Piedade, Nishita Meshram |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Embryo Nonmammalian MMP2 genetic structures Gene Expression lcsh:Medicine Eye Basement Membrane Retina Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Vasculogenesis Live cell imaging Morphogenesis medicine Animals lcsh:Science Zebrafish Loss function Basement membrane Coloboma Multidisciplinary biology Disease model PAX2 Transcription Factor lcsh:R Gene Expression Regulation Developmental Retinal Zebrafish Proteins biology.organism_classification medicine.disease eye diseases Cell biology 030104 developmental biology medicine.anatomical_structure chemistry Mutation Matrix Metalloproteinase 2 Biological metamorphosis lcsh:Q sense organs 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-66451-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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