2026-04-29T04:00:28Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/166412024-09-27T08:47:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Lange, Martin
author
Ohnesorge, Nils
author
Hoffmann, Dennis
author
Rocha, Susana F
author
Benedito, Rui
author
Siekmann, Arndt F
funder
Max Planck Society
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2023-11-06T11:48:32Z
2023-11-06T11:48:32Z
2022-06
Dev Biol. 2022 Jun:486:26-43.
http://hdl.handle.net/20.500.12105/16641
35337795
10.1016/j.ydbio.2022.03.006
1095-564X
Developmental biology
The formation of appropriately patterned blood vessel networks requires endothelial cell migration and proliferation. Signaling through the Vascular Endothelial Growth Factor A (VEGFA) pathway is instrumental in coordinating these processes. mRNA splicing generates short (diffusible) and long (extracellular matrix bound) Vegfa isoforms. The differences between these isoforms in controlling cellular functions are not understood. In zebrafish, vegfaa generates short and long isoforms, while vegfab only generates long isoforms. We found that mutations in vegfaa had an impact on endothelial cell (EC) migration and proliferation. Surprisingly, mutations in vegfab more strongly affected EC proliferation in distinct blood vessels, such as intersegmental blood vessels in the zebrafish trunk and central arteries in the head. Analysis of downstream signaling pathways revealed no change in MAPK (ERK) activation, while inhibiting PI3 kinase signaling phenocopied vegfab mutant phenotypes in affected blood vessels. Together, these results suggest that extracellular matrix bound Vegfa might act through PI3K signaling to control EC proliferation in a distinct set of blood vessels during angiogenesis.
eng
Zebrafish mutants in vegfab can affect endothelial cell proliferation without altering ERK phosphorylation and are phenocopied by loss of PI3K signaling.
journal article
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URL
https://repisalud.isciii.es/bitstreams/df8c62fa-e3cc-487e-80ee-addee74d0b60/download
File
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application/pdf
Zebrafish mutants in vegfab_Dev BioL_2022.pdf
URL
https://repisalud.isciii.es/bitstreams/beda29ab-a0ce-4385-a4eb-bc09f49b336e/download
File
MD5
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text/plain
Zebrafish mutants in vegfab_Dev BioL_2022.pdf.txt