Title |
VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling
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Published in |
Nature Cell Biology, September 2011
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DOI | 10.1038/ncb2331 |
Pubmed ID | |
Authors |
Tuomas Tammela, Georgia Zarkada, Harri Nurmi, Lars Jakobsson, Krista Heinolainen, Denis Tvorogov, Wei Zheng, Claudio A. Franco, Aino Murtomäki, Evelyn Aranda, Naoyuki Miura, Seppo Ylä-Herttuala, Marcus Fruttiger, Taija Mäkinen, Anne Eichmann, Jeffrey W. Pollard, Holger Gerhardt, Kari Alitalo |
Abstract |
Angiogenesis, the growth of new blood vessels, involves specification of endothelial cells to tip cells and stalk cells, which is controlled by Notch signalling, whereas vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 have been implicated in angiogenic sprouting. Surprisingly, we found that endothelial deletion of Vegfr3, but not VEGFR-3-blocking antibodies, postnatally led to excessive angiogenic sprouting and branching, and decreased the level of Notch signalling, indicating that VEGFR-3 possesses passive and active signalling modalities. Furthermore, macrophages expressing the VEGFR-3 and VEGFR-2 ligand VEGF-C localized to vessel branch points, and Vegfc heterozygous mice exhibited inefficient angiogenesis characterized by decreased vascular branching. FoxC2 is a known regulator of Notch ligand and target gene expression, and Foxc2(+/-);Vegfr3(+/-) compound heterozygosity recapitulated homozygous loss of Vegfr3. These results indicate that macrophage-derived VEGF-C activates VEGFR-3 in tip cells to reinforce Notch signalling, which contributes to the phenotypic conversion of endothelial cells at fusion points of vessel sprouts. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | <1% |
Germany | 2 | <1% |
Switzerland | 1 | <1% |
Portugal | 1 | <1% |
Iran, Islamic Republic of | 1 | <1% |
Austria | 1 | <1% |
Korea, Republic of | 1 | <1% |
Belgium | 1 | <1% |
Unknown | 336 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 88 | 25% |
Researcher | 75 | 22% |
Student > Master | 36 | 10% |
Student > Bachelor | 28 | 8% |
Student > Doctoral Student | 19 | 5% |
Other | 57 | 16% |
Unknown | 44 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 142 | 41% |
Biochemistry, Genetics and Molecular Biology | 68 | 20% |
Medicine and Dentistry | 40 | 12% |
Engineering | 14 | 4% |
Neuroscience | 6 | 2% |
Other | 26 | 7% |
Unknown | 51 | 15% |