TRPC1 Is Essential for In Vivo Angiogenesis in Zebrafish

Yu, P.C., Gu, S.Y., Bu, J.W., and Du, J.L.
Circulation research   106(7): 1221-1232 (Journal)
Registered Authors
Du, Jiu Lin
TRPC1, VEGF, ISV, angiogenesis, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Blood Vessels/embryology
  • Blood Vessels/metabolism*
  • Cell Movement
  • Cell Proliferation
  • Endothelial Cells/metabolism*
  • Endothelial Cells/transplantation
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Microscopy, Confocal
  • Microscopy, Video
  • Neovascularization, Physiologic*
  • Oligonucleotides, Antisense/metabolism
  • Phosphorylation
  • Pseudopodia/metabolism
  • RNA, Messenger/metabolism
  • Signal Transduction
  • TRPC Cation Channels/genetics
  • TRPC Cation Channels/metabolism*
  • Vascular Endothelial Growth Factor A/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
20185799 Full text @ Circ. Res.
Rationale: Wiring vascular and neural networks are known to share common molecular signaling pathways. Activation of transient receptor potential type C channels (TRPCs) has recently been shown to underlie chemotropic guidance of neural axons. It is thus of interest to examine whether TRPCs are also involved in vascular development. Objective: To determine the role of TRPC1 in angiogenesis in vivo during zebrafish development. Methods and Results: Knockdown of zebrafish trpc1 by antisense morpholino oligonucleotides severely disrupted angiogenic sprouting of intersegmental vessels (ISVs) in zebrafish larvae. This angiogenic defect was prevented by overexpression of a morpholino oligonucleotide-resistant form of zebrafish trpc1 mRNA. Cell transplantation analysis showed that this requirement of Trpc1 for ISV growth was endothelial cell-autonomous. In vivo, time-lapse imaging further revealed that the angiogenic defect was attributable to impairment of filopodia extension, migration, and proliferation of ISV tip cells. Furthermore, Trpc1 acted synergistically with vascular endothelial growth factor A (Vegf-a) in controlling ISV growth, and appeared to be downstream to Vegf-a in controlling angiogenesis, as evidence by the findings that Trpc1 was required for Vegf-a-induced ectopic angiogenesis of subintestinal veins and phosphorylation of extracellular signal-regulated kinase. Conclusions: These results provide the first in vivo evidence that TRPC1 is essential for angiogenesis, reminiscent of the role of TRPCs in axon guidance. It implicates that TRPC1 may represent a potential target for treating pathological angiogenesis.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes