PUBLICATION

Selective Requirements for Vascular Endothelial Cells and Circulating Factors in the Regulation of Retinal Neurogenesis

Authors
Dhakal, S., Rotem-Bamberger, S., Sejd, J.R., Sebbagh, M., Ronin, N., Frey, R.A., Beitsch, M., Batty, M., Taler, K., Blackerby, J.F., Inbal, A., Stenkamp, D.L.
ID
ZDB-PUB-210428-13
Date
2021
Source
Frontiers in cell and developmental biology   9: 628737 (Journal)
Registered Authors
Frey, Ruth, Stenkamp, Deborah L.
Keywords
circulation, development, differentiation, eye, neurogenesis, retina, vascular endothelial cell, zebrafish
MeSH Terms
none
PubMed
33898420 Full text @ Front Cell Dev Biol
Abstract
Development of the vertebrate eye requires signaling interactions between neural and non-neural tissues. Interactions between components of the vascular system and the developing neural retina have been difficult to decipher, however, due to the challenges of untangling these interactions from the roles of the vasculature in gas exchange. Here we use the embryonic zebrafish, which is not yet reliant upon hemoglobin-mediated oxygen transport, together with genetic strategies for (1) temporally-selective depletion of vascular endothelial cells, (2) elimination of blood flow through the circulation, and (3) elimination of cells of the erythroid lineage, including erythrocytes. The retinal phenotypes in these genetic systems were not identical, with endothelial cell-depleted retinas displaying laminar disorganization, cell death, reduced proliferation, and reduced cell differentiation. In contrast, the lack of blood flow resulted in a milder retinal phenotype showing reduced proliferation and reduced cell differentiation, indicating that an endothelial cell-derived factor(s) is/are required for laminar organization and cell survival. The lack of erythrocytes did not result in an obvious retinal phenotype, confirming that defects in retinal development that result from vascular manipulations are not due to poor gas exchange. These findings underscore the importance of the cardiovascular system supporting and controlling retinal development in ways other than supplying oxygen. In addition, these findings identify a key developmental window for these interactions and point to distinct functions for vascular endothelial cells vs. circulating factors.
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Expression
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Phenotype
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
c264TgTransgenic Insertion
    m651
      		Point Mutation
      mn0031GtTransgenic Insertion
      mu101TgTransgenic Insertion
        s843TgTransgenic Insertion
          sd2TgTransgenic Insertion
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            Human Disease / Model
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            Sequence Targeting Reagents
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            Antibodies
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            DsRedEFGDsRed
            EGFPEFGEGFP
            GAL4FFEFGGAL4FF
            mCherryEFGmCherry
            mRFP1EFGmRFP1
            NTREFGNTR
            1 - 6 of 6
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            Citation
            Dhakal, S., Rotem-Bamberger, S., Sejd, J.R., Sebbagh, M., Ronin, N., Frey, R.A., Beitsch, M., Batty, M., Taler, K., Blackerby, J.F., Inbal, A., Stenkamp, D.L. (2021) Selective Requirements for Vascular Endothelial Cells and Circulating Factors in the Regulation of Retinal Neurogenesis. Frontiers in cell and developmental biology. 9:628737.