PUBLICATION
Etv2 and Fli1b Function Together as Key Regulators of Vasculogenesis and Angiogenesis
- Authors
- Craig, M.P., Grajevskaja, V., Liao, H.K., Balciuniene, J., Ekker, S.C., Park, J.S., Essner, J.J., Balciunas, D., Sumanas, S.
- ID
- ZDB-PUB-150301-12
- Date
- 2015
- Source
- Arterioscler. Thromb. Vasc. Biol. 35(4): 865-76 (Journal)
- Registered Authors
- Keywords
- proto-oncogene proteins c-ETS, angiogenesis, ETS transcription factor, vasculogenesis, zebrafish
- MeSH Terms
-
- Angiogenic Proteins/genetics
- Angiogenic Proteins/metabolism*
- Animals
- Animals, Genetically Modified
- Apoptosis
- Binding Sites
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/metabolism
- Endothelial Cells/metabolism*
- Gene Expression Regulation, Developmental
- Genotype
- Morpholinos/metabolism
- Mutation
- Neovascularization, Physiologic*
- Phenotype
- Promoter Regions, Genetic
- Proto-Oncogene Protein c-fli-1/genetics
- Proto-Oncogene Protein c-fli-1/metabolism*
- Signal Transduction
- Time Factors
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Transcription, Genetic
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 25722433 Full text @ Arterioscler. Thromb. Vasc. Biol.
Citation
Craig, M.P., Grajevskaja, V., Liao, H.K., Balciuniene, J., Ekker, S.C., Park, J.S., Essner, J.J., Balciunas, D., Sumanas, S. (2015) Etv2 and Fli1b Function Together as Key Regulators of Vasculogenesis and Angiogenesis. Arterioscler. Thromb. Vasc. Biol.. 35(4):865-76.
Abstract
Objective The E26 transformation-specific domain transcription factor Etv2/Etsrp/ER71 is a master regulator of vascular endothelial differentiation during vasculogenesis, although its later role in sprouting angiogenesis remains unknown. Here, we investigated in the zebrafish model a role for Etv2 and related E26 transformation-specific factors, Fli1a and Fli1b in developmental angiogenesis.
Approach and results Zebrafish fli1a and fli1b mutants were obtained using transposon-mediated gene trap approach. Individual fli1a and fli1b homozygous mutant embryos display normal vascular patterning, yet the angiogenic recovery observed in older etv2 mutant embryos does not occur in embryos lacking both etv2 and fli1b. Etv2 and fli1b double-deficient embryos fail to form any angiogenic sprouts and show greatly increased apoptosis throughout the axial vasculature. In contrast, fli1a mutation did not affect the recovery of etv2 mutant phenotype. Overexpression analyses indicate that both etv2 and fli1b, but not fli1a, induce the expression of multiple vascular markers and of each other. Temporal inhibition of Etv2 function using photoactivatable morpholinos indicates that the function of Etv2 and Fli1b during angiogenesis is independent from the early requirement of Etv2 during vasculogenesis. RNA-Seq analysis and chromatin immunoprecipitation suggest that Etv2 and Fli1b share the same transcriptional targets and bind to the same E26 transformation-specific sites.
Conclusions Our data argue that there are 2 phases of early vascular development with distinct requirements of E26 transformation-specific transcription factors. Etv2 alone is required for early vasculogenesis, whereas Etv2 and Fli1b function redundantly during late vasculogenesis and early embryonic angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping