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Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development
Neil I Bower1, Adam J Vogrin2, Ludovic Le Guen1
1Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
Development (Cambridge, England)
|January 15, 2017
Summary
Vascular endothelial growth factor D (Vegfd) is essential for facial lymphangiogenesis and cooperates with Vegfc in embryonic lymphatic development. Vegfd also plays compensatory roles in blood vessel angiogenesis.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Vascular endothelial growth factors (VEGFs) regulate blood vessel and lymphatic vessel formation.
- Vegfa and Vegfc are known regulators of angiogenesis and lymphangiogenesis in zebrafish.
- Vegfd was previously considered dispensable for vertebrate vascular development.
Purpose of the Study:
- To investigate the role of Vegfd in zebrafish vascular development.
- To determine the functional relationship between Vegfc and Vegfd in lymphangiogenesis.
- To explore Vegfd's involvement in angiogenesis, particularly in response to Flt1 or Dll4 depletion.
Main Methods:
- Generation of a zebrafish vegfd mutant using genome editing.
- Analysis of facial and trunk lymphatic vasculature development in vegfd mutants.
- Epistasis and biochemical binding assays to elucidate signaling pathways.
Main Results:
- Vegfd mutants exhibit significant defects in facial lymphangiogenesis, independent of Vegfc.
- Vegfc and Vegfd cooperatively regulate lymphangiogenesis throughout the embryo.
- Vegfd and Vegfc redundantly influence artery hyperbranching phenotypes upon Flt1 or Dll4 depletion, potentially via Kdr (Vegfr2).
Conclusions:
- Vegfd is not dispensable but plays context-specific indispensable roles in lymphangiogenesis.
- Vegfd and Vegfc function cooperatively and redundantly in lymphatic and blood vessel development.
- Vegfd contributes to both primary and secondary angiogenesis, highlighting its broader importance than previously recognized.
