TRPC1 is essential for in vivo angiogenesis in zebrafish.
BACKGROUND
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.


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.
Yu
Peng-chun
PC
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Gu
Shan-ye
SY
Bu
Ji-wen
JW
Du
Jiu-lin
JL
D000818:Animals; D030801:Animals, Genetically Modified; D001808:Blood Vessels / Q000196:embryology / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism* / Q000637:transplantation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D018919:Neovascularization, Physiologic; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010766:Phosphorylation; D011554:Pseudopodia / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D050052:TRPC Cation Channels; D042461:Vascular Endothelial Growth Factor A; C096351:transient receptor potential cation channel, subfamily C, member 1; D048049:Extracellular Signal-Regulated MAP Kinases