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  Regulation of Vegf signaling by natural and synthetic ligands

Rossi, A., Gauvrit, S., Marass, M., Pan, L., Moens, C. B., & Stainier, D. Y. (2016). Regulation of Vegf signaling by natural and synthetic ligands. BLOOD, 128(19), 2359-2366. doi:10.1182/blood-2016-04-711192.

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Genre: Journal Article

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 Creators:
Rossi, Andrea1, Author              
Gauvrit, Sebastien1, Author              
Marass, Michele1, Author              
Pan, Luyuan, Author
Moens, Cecilia B., Author
Stainier, Didier Y.R.1, Author              
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              

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Free keywords: GROWTH-FACTOR VEGF; ZEBRAFISH; BINDING; ANGIOGENESIS; ARTERIES; IDENTIFICATION; VASCULATURE; GENERATION; STRATEGY; SYSTEMHematology;
 Abstract: The mechanisms that allow cells to bypass anti-vascular endothelial growth factor A (VEGFA) therapy remain poorly understood. Here we use zebrafish to investigate this question and first show that vegfaa mutants display a severe vascular phenotype that can surprisingly be rescued to viability by vegfaa messenger RNA injections at the 1-cell stage. Using vegfaa mutants as an in vivo test tube, we found that zebrafish Vegfbb, Vegfd, and Pgfb can also rescue these animals to viability. Taking advantage of a new vegfr1 tyrosine kinase-deficient mutant, we determined that Pgfb rescues vegfaa mutants via Vegfr1. Altogether, these data reveal potential resistance routes against current anti-VEGFA therapies. In order to circumvent this resistance, we engineered and validated new dominant negative Vegfa molecules that by trapping Vegf family members can block vascular development. Thus, our results show that Vegfbb, Vegfd, and Pgfb can sustain vascular development in the absence of VegfA, and our newly engineered Vegf molecules expand the toolbox for basic research and antiangiogenic therapy.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: BLOOD
Source Genre: Journal
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Publ. Info: 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA : AMER SOC HEMATOLOGY
Pages: - Volume / Issue: 128 (19) Sequence Number: - Start / End Page: 2359 - 2366 Identifier: ISSN: 0006-4971