| RRC ID |
86760
|
| Author |
Hasan SS, Tsaryk R, Lange M, Wisniewski L, Moore JC, Lawson ND, Wojciechowska K, Schnittler H, Siekmann AF.
|
| Title |
Endothelial Notch signalling limits angiogenesis via control of artery formation.
|
| Journal |
Nat Cell Biol
|
| Abstract |
Angiogenic sprouting needs to be tightly controlled. It has been suggested that the Notch ligand dll4 expressed in leading tip cells restricts angiogenesis by activating Notch signalling in trailing stalk cells. Here, we show using live imaging in zebrafish that activation of Notch signalling is rather required in tip cells. Notch activation initially triggers expression of the chemokine receptor cxcr4a. This allows for proper tip cell migration and connection to the pre-existing arterial circulation, ultimately establishing functional arterial-venous blood flow patterns. Subsequently, Notch signalling reduces cxcr4a expression, thereby preventing excessive blood vessel growth. Finally, we find that Notch signalling is dispensable for limiting blood vessel growth during venous plexus formation that does not generate arteries. Together, these findings link the role of Notch signalling in limiting angiogenesis to its role during artery formation and provide a framework for our understanding of the mechanisms underlying blood vessel network expansion and maturation.
|
| Volume |
19(8)
|
| Pages |
928-940
|
| Published |
2017-8-1
|
| DOI |
10.1038/ncb3574
|
| PII |
ncb3574
|
| PMID |
28714969
|
| PMC |
PMC5534340
|
| MeSH |
Animals
Animals, Genetically Modified
Arteries / cytology
Arteries / metabolism*
Cell Movement
Cells, Cultured
Endothelial Cells / metabolism*
Gene Expression Regulation, Developmental
Genotype
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Human Umbilical Vein Endothelial Cells / metabolism
Humans
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism
Membrane Proteins / genetics
Membrane Proteins / metabolism
Microscopy, Fluorescence
Microscopy, Video
Neovascularization, Physiologic*
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Phenotype
Receptor, Notch1 / genetics
Receptor, Notch1 / metabolism*
Receptors, CXCR4 / genetics
Receptors, CXCR4 / metabolism
Signal Transduction
Time Factors
Time-Lapse Imaging
Transfection
Zebrafish / genetics
Zebrafish / metabolism
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism*
|
| IF |
20.042
|
| Resource |
| Zebrafish |
UAS:GFP |
