Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS Development
An emerging area of interest in Neuroscience is the cellular relationship between glia and blood vessels, as many of the presumptive support roles of glia require an association with the vasculature. These interactions are best studied in vivo and great strides have been made using mice to longitudi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.654338/full |
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| author | Robyn A. Umans Carolyn Pollock William A. Mills Kareem C. Clark Y. Albert Pan Y. Albert Pan Y. Albert Pan Harald Sontheimer Harald Sontheimer |
| author_facet | Robyn A. Umans Carolyn Pollock William A. Mills Kareem C. Clark Y. Albert Pan Y. Albert Pan Y. Albert Pan Harald Sontheimer Harald Sontheimer |
| author_sort | Robyn A. Umans |
| collection | DOAJ |
| description | An emerging area of interest in Neuroscience is the cellular relationship between glia and blood vessels, as many of the presumptive support roles of glia require an association with the vasculature. These interactions are best studied in vivo and great strides have been made using mice to longitudinally image glial-vascular interactions. However, these methods are cumbersome for developmental studies, which could benefit from a more accessible system. Zebrafish (Danio rerio) are genetically tractable vertebrates, and given their translucency, are readily amenable for daily live imaging studies. We set out to examine whether zebrafish glia have conserved traits with mammalian glia regarding their ability to interact with and maintain the developing brain vasculature. We utilized transgenic zebrafish strains in which oligodendrocyte transcription factor 2 (olig2) and glial fibrillary acidic protein (gfap) identify different glial populations in the zebrafish brain and document their corresponding relationship with brain blood vessels. Our results demonstrate that olig2+ and gfap+ zebrafish glia have distinct lineages and each interact with brain vessels as previously observed in mouse brain. Additionally, we manipulated these relationships through pharmacological and genetic approaches to distinguish the roles of these cell types during blood vessel development. olig2+ glia use blood vessels as a pathway during their migration and Wnt signaling inhibition decreases their single-cell vessel co-option. By contrast, the ablation of gfap+ glia at the beginning of CNS angiogenesis impairs vessel development through a reduction in Vascular endothelial growth factor (Vegf), supporting a role for gfap+ glia during new brain vessel formation in zebrafish. This data suggests that zebrafish glia, akin to mammalian glia, have different lineages that show diverse interactions with blood vessels, and are a suitable model for elucidating glial-vascular relationships during vertebrate brain development. |
| first_indexed | 2024-12-18T01:25:13Z |
| format | Article |
| id | doaj.art-535036971df04f15b296fee2793a73d4 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-18T01:25:13Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-535036971df04f15b296fee2793a73d42022-12-21T21:25:45ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-06-01910.3389/fcell.2021.654338654338Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS DevelopmentRobyn A. Umans0Carolyn Pollock1William A. Mills2Kareem C. Clark3Y. Albert Pan4Y. Albert Pan5Y. Albert Pan6Harald Sontheimer7Harald Sontheimer8Glial Biology in Health, Disease, and Cancer Center, The Fralin Biomedical Research Institute at VTC, Roanoke, VA, United StatesSchool of Neuroscience, Virginia Tech, Blacksburg, VA, United StatesGlial Biology in Health, Disease, and Cancer Center, The Fralin Biomedical Research Institute at VTC, Roanoke, VA, United StatesCenter for Neurobiology Research, The Fralin Biomedical Research Institute at VTC, Roanoke, VA, United StatesCenter for Neurobiology Research, The Fralin Biomedical Research Institute at VTC, Roanoke, VA, United StatesDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United StatesDepartment of Psychiatry and Behavioral Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, United StatesGlial Biology in Health, Disease, and Cancer Center, The Fralin Biomedical Research Institute at VTC, Roanoke, VA, United StatesDepartment of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, United StatesAn emerging area of interest in Neuroscience is the cellular relationship between glia and blood vessels, as many of the presumptive support roles of glia require an association with the vasculature. These interactions are best studied in vivo and great strides have been made using mice to longitudinally image glial-vascular interactions. However, these methods are cumbersome for developmental studies, which could benefit from a more accessible system. Zebrafish (Danio rerio) are genetically tractable vertebrates, and given their translucency, are readily amenable for daily live imaging studies. We set out to examine whether zebrafish glia have conserved traits with mammalian glia regarding their ability to interact with and maintain the developing brain vasculature. We utilized transgenic zebrafish strains in which oligodendrocyte transcription factor 2 (olig2) and glial fibrillary acidic protein (gfap) identify different glial populations in the zebrafish brain and document their corresponding relationship with brain blood vessels. Our results demonstrate that olig2+ and gfap+ zebrafish glia have distinct lineages and each interact with brain vessels as previously observed in mouse brain. Additionally, we manipulated these relationships through pharmacological and genetic approaches to distinguish the roles of these cell types during blood vessel development. olig2+ glia use blood vessels as a pathway during their migration and Wnt signaling inhibition decreases their single-cell vessel co-option. By contrast, the ablation of gfap+ glia at the beginning of CNS angiogenesis impairs vessel development through a reduction in Vascular endothelial growth factor (Vegf), supporting a role for gfap+ glia during new brain vessel formation in zebrafish. This data suggests that zebrafish glia, akin to mammalian glia, have different lineages that show diverse interactions with blood vessels, and are a suitable model for elucidating glial-vascular relationships during vertebrate brain development.https://www.frontiersin.org/articles/10.3389/fcell.2021.654338/fullgliavasculaturezebrafishbrain developmentangiogenesis |
| spellingShingle | Robyn A. Umans Carolyn Pollock William A. Mills Kareem C. Clark Y. Albert Pan Y. Albert Pan Y. Albert Pan Harald Sontheimer Harald Sontheimer Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS Development Frontiers in Cell and Developmental Biology glia vasculature zebrafish brain development angiogenesis |
| title | Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS Development |
| title_full | Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS Development |
| title_fullStr | Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS Development |
| title_full_unstemmed | Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS Development |
| title_short | Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS Development |
| title_sort | using zebrafish to elucidate glial vascular interactions during cns development |
| topic | glia vasculature zebrafish brain development angiogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.654338/full |
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