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Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development
- Source :
- Development.
- Publication Year :
- 2017
- Publisher :
- The Company of Biologists, 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, the formation of 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 indispensible and also compensatory roles during both blood vessel angiogenesis and lymphangiogenesis.
- Subjects :
- 0301 basic medicine
Angiogenesis
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor D
Neovascularization, Physiologic
Models, Biological
Neovascularization
03 medical and health sciences
medicine
Animals
Lymphangiogenesis
Molecular Biology
Zebrafish
Sequence Deletion
Vascular Endothelial Growth Factor Receptor-1
biology
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Zebrafish Proteins
biology.organism_classification
Vascular Endothelial Growth Factor Receptor-2
FLT4
Up-Regulation
Cell biology
Vascular endothelial growth factor A
030104 developmental biology
Vascular endothelial growth factor C
Mutagenesis
Immunology
medicine.symptom
Signal Transduction
Developmental Biology
Subjects
Details
- ISSN :
- 14779129 and 09501991
- Database :
- OpenAIRE
- Journal :
- Development
- Accession number :
- edsair.doi.dedup.....d747d54c39875371f57991d7ba5d050b