Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos
Angiogenesis, the outgrowth of new blood vessels from existing vasculature, is critical during development, tissue formation, and wound healing. In response to vascular endothelial growth factors (VEGFs), endothelial cells are activated to proliferate and move towards the signal, extending the vesse...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.845407/full |
| _version_ | 1818474172160933888 |
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| author | Cassandra J. Field Alexis M. Perez Taryn Samet Victoria Ricles M. Kathryn Iovine Linda J. Lowe-Krentz |
| author_facet | Cassandra J. Field Alexis M. Perez Taryn Samet Victoria Ricles M. Kathryn Iovine Linda J. Lowe-Krentz |
| author_sort | Cassandra J. Field |
| collection | DOAJ |
| description | Angiogenesis, the outgrowth of new blood vessels from existing vasculature, is critical during development, tissue formation, and wound healing. In response to vascular endothelial growth factors (VEGFs), endothelial cells are activated to proliferate and move towards the signal, extending the vessel. These events are directed by VEGF-VEGF receptor (Vegfr2) signal transduction, which in turn is modulated by heparan sulfate proteoglycans (HSPGs). HSPGs are glycoproteins covalently attached to HS glycosaminoglycan chains. Transmembrane protein 184a (Tmem184a) has been recently identified as a heparin receptor, which is believed to bind heparan sulfate chains in vivo. Therefore, Tmem184a has the potential to fine-tune interactions between VEGF and HS, modulating Vegfr2-dependent angiogenesis. The function of Tmem184a has been investigated in the regenerating zebrafish caudal fin, but its role has yet to be evaluated during developmental angiogenesis. Here we provide insights into how Tmem184a contributes to the proper formation of the vasculature in zebrafish embryos. First, we find that knockdown of Tmem184a causes a reduction in the number of intact intersegmental vessels (ISVs) in the zebrafish embryo. This phenotype mimics that of vegfr2b knockout mutants, which have previously been shown to exhibit severe defects in ISV development. We then test the importance of HS interactions by removing the binding domain within the Tmem184a protein, which has a negative effect on angiogenesis. Tmem184a is found to act synergistically with Vegfr2b, indicating that the two gene products function in a common pathway to modulate angiogenesis. Moreover, we find that knockdown of Tmem184a leads to an increase in endothelial cell proliferation but a decrease in the amount of VE-cadherin present. Together, these findings suggest that Tmem184a is necessary for ISVs to organize into mature, complete vessels. |
| first_indexed | 2024-04-14T04:34:25Z |
| format | Article |
| id | doaj.art-e1b209cf4a514f1290010b29526cc301 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-14T04:34:25Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-e1b209cf4a514f1290010b29526cc3012022-12-22T02:11:57ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-09-011310.3389/fphys.2022.845407845407Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryosCassandra J. FieldAlexis M. PerezTaryn SametVictoria RiclesM. Kathryn IovineLinda J. Lowe-KrentzAngiogenesis, the outgrowth of new blood vessels from existing vasculature, is critical during development, tissue formation, and wound healing. In response to vascular endothelial growth factors (VEGFs), endothelial cells are activated to proliferate and move towards the signal, extending the vessel. These events are directed by VEGF-VEGF receptor (Vegfr2) signal transduction, which in turn is modulated by heparan sulfate proteoglycans (HSPGs). HSPGs are glycoproteins covalently attached to HS glycosaminoglycan chains. Transmembrane protein 184a (Tmem184a) has been recently identified as a heparin receptor, which is believed to bind heparan sulfate chains in vivo. Therefore, Tmem184a has the potential to fine-tune interactions between VEGF and HS, modulating Vegfr2-dependent angiogenesis. The function of Tmem184a has been investigated in the regenerating zebrafish caudal fin, but its role has yet to be evaluated during developmental angiogenesis. Here we provide insights into how Tmem184a contributes to the proper formation of the vasculature in zebrafish embryos. First, we find that knockdown of Tmem184a causes a reduction in the number of intact intersegmental vessels (ISVs) in the zebrafish embryo. This phenotype mimics that of vegfr2b knockout mutants, which have previously been shown to exhibit severe defects in ISV development. We then test the importance of HS interactions by removing the binding domain within the Tmem184a protein, which has a negative effect on angiogenesis. Tmem184a is found to act synergistically with Vegfr2b, indicating that the two gene products function in a common pathway to modulate angiogenesis. Moreover, we find that knockdown of Tmem184a leads to an increase in endothelial cell proliferation but a decrease in the amount of VE-cadherin present. Together, these findings suggest that Tmem184a is necessary for ISVs to organize into mature, complete vessels.https://www.frontiersin.org/articles/10.3389/fphys.2022.845407/fullheparan-binding proteinheparan sulfate proteoglycansvascular endothelial growth factorTMEM184Aangiogenesis |
| spellingShingle | Cassandra J. Field Alexis M. Perez Taryn Samet Victoria Ricles M. Kathryn Iovine Linda J. Lowe-Krentz Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos Frontiers in Physiology heparan-binding protein heparan sulfate proteoglycans vascular endothelial growth factor TMEM184A angiogenesis |
| title | Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos |
| title_full | Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos |
| title_fullStr | Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos |
| title_full_unstemmed | Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos |
| title_short | Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos |
| title_sort | involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos |
| topic | heparan-binding protein heparan sulfate proteoglycans vascular endothelial growth factor TMEM184A angiogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.845407/full |
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