PUBLICATION

The zebrafish Tie2 signaling controls tip cell behaviors and acts synergistically with Vegf pathway in developmental angiogenesis

Authors
Li, W., Chen, J., Deng, M., Jing, Q.
ID
ZDB-PUB-140710-15
Date
2014
Source
Acta biochimica et biophysica Sinica   46(8): 641-6 (Journal)
Registered Authors
Deng, Min
Keywords
Tie2, Vegf, angiogenesis, tip cell
MeSH Terms
  • Animals
  • Base Sequence
  • DNA Primers
  • In Situ Hybridization
  • Neovascularization, Physiologic*
  • RNA, Messenger/genetics
  • Receptor, TIE-2/genetics
  • Receptor, TIE-2/metabolism
  • Signal Transduction*
  • Vascular Endothelial Growth Factor A/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
25001479 Full text @ Acta. Biochim. Biophys. Sin (Shanghai)
Abstract
Angiogenesis process in development is temporally accurate, and involves sprouting, subsequent endothelial cell proliferation, and migration. Tip cells, sensing the extracellular cues, play an important role in this process. Although it is known that several pathways including vascular endothelial growth factor (VEGF) and Notch control tip cell behaviors, the signaling process is largely unknown. Here we showed that an endothelial tyrosine kinase receptor-Tie2 was required for intersegmental vessel (ISV) growth and essential for the sprouting, migration, and proliferation of tip cells with morpholino knockdown strategy in zebrafish. Knockdown of vegf effectively reduced tie2 mRNA level, and tie2 knockdown efficiently blocked the vegf over-expression induced tyrosine kinase receptor-VEGFR1 (flk1) expression, which suggested that the function of Tie2 may be linked to the downstream of VEGF signaling pathway. Furthermore, we found that the embryos displayed normal ISV growth when injected with tie2 or vegf morpholino alone at a low dose, while co-knockdown of them resulted in a severe ISV defect, indicating a synergistic role in ISV formation. These observations demonstrate that Tie2 is an important regulator of tip cell behaviors. Moreover, these findings provide in vivo evidence that Tie2 acts coordinately with Vegf signaling to control angiogenesis.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping