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Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development.
- Source :
-
Development (Cambridge, England) [Development] 2017 Feb 01; Vol. 144 (3), pp. 507-518. Date of Electronic Publication: 2017 Jan 13. - Publication Year :
- 2017
-
Abstract
- Vascular endothelial growth factors (VEGFs) control angiogenesis and lymphangiogenesis during development and in pathological conditions. In the zebrafish trunk, Vegfa controls the formation of intersegmental arteries by primary angiogenesis and Vegfc is essential for secondary angiogenesis, giving rise to veins and lymphatics. Vegfd has been largely thought of as dispensable for vascular development in vertebrates. Here, we generated a zebrafish vegfd mutant by genome editing. vegfd mutants display significant defects in facial lymphangiogenesis independent of vegfc function. Strikingly, we find that vegfc and vegfd cooperatively control lymphangiogenesis throughout the embryo, including during the formation of the trunk lymphatic vasculature. Interestingly, we find that vegfd and vegfc also redundantly drive artery hyperbranching phenotypes observed upon depletion of Flt1 or Dll4. Epistasis and biochemical binding assays suggest that, during primary angiogenesis, Vegfd influences these phenotypes through Kdr (Vegfr2) rather than Flt4 (Vegfr3). These data demonstrate that, rather than being dispensable during development, Vegfd plays context-specific indispensable and also compensatory roles during both blood vessel angiogenesis and lymphangiogenesis.<br /> (© 2017. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Intracellular Signaling Peptides and Proteins genetics
Intracellular Signaling Peptides and Proteins physiology
Lymphangiogenesis genetics
Membrane Proteins genetics
Membrane Proteins physiology
Models, Biological
Mutagenesis
Neovascularization, Physiologic genetics
Sequence Deletion
Signal Transduction
Up-Regulation
Vascular Endothelial Growth Factor C genetics
Vascular Endothelial Growth Factor C physiology
Vascular Endothelial Growth Factor D genetics
Vascular Endothelial Growth Factor Receptor-1 genetics
Vascular Endothelial Growth Factor Receptor-1 physiology
Vascular Endothelial Growth Factor Receptor-2 genetics
Vascular Endothelial Growth Factor Receptor-2 physiology
Zebrafish genetics
Zebrafish Proteins genetics
Lymphangiogenesis physiology
Neovascularization, Physiologic physiology
Vascular Endothelial Growth Factor D physiology
Zebrafish embryology
Zebrafish physiology
Zebrafish Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 144
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 28087639
- Full Text :
- https://doi.org/10.1242/dev.146969