2014 Fiscal Year Final Research Report
Crosstalk between endothelial tip cells and neurons in the developing retina
| Project Area | Vasculo-neural wiring and their interdependent crosstalk |
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| Project/Area Number |
22122002
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2010-04-01 – 2015-03-31
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| Keywords | VEGF / VEGFR2 / 網膜 / エンドサイトーシス / 神経 / 血管新生 |
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| Outline of Final Research Achievements |
During development, neurons guide and attract blood vessels and consequently the parallelism of these two is established. Here we identified a non-canonical neurovascular interaction in eye development. VEGFR2, a critical endothelial receptor for VEGF, was more abundantly expressed in retinal neurons than in endothelial cells including endothelial tip cells. Genetic deletion of VEGFR2 in neurons caused misdirected angiogenesis toward neurons resulting in abnormally increased vascular density around neurons. Further genetic experiments revealed that this misdirected angiogenesis was attributable to an excessive amount of VEGF protein around neurons caused by insufficient engulfment of VEGF by VEGFR2-deficient neurons. Moreover, absence of neuronal VEGFR2 caused misdirected regenerative angiogenesis in ischemic retinopathy. Thus, this study revealed novel neurovascular crosstalk and unprecedented cellular regulation of VEGF: retinal neurons titrate VEGF to limit neuronal vascularization.
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| Free Research Field |
医歯薬学
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