Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis

@article{Hellstrm2007Dll4ST,
  title={Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis},
  author={Mats Hellstr{\"o}m and Li-Kun Phng and Jennifer J. Hofmann and Elisabet Wallgard and Leigh Coultas and Per Lindblom and Jackelyn A. Alva and A K Nilsson and Linda Karlsson and Nicholas R. Gaiano and Keejung Yoon and Janet Rossant and M. Luisa Iruela-Arispe and Mattias Kal{\'e}n and Holger Gerhardt and Christer Betsholtz},
  journal={Nature},
  year={2007},
  volume={445},
  pages={776-780}
}
In sprouting angiogenesis, specialized endothelial tip cells lead the outgrowth of blood-vessel sprouts towards gradients of vascular endothelial growth factor (VEGF)-A. VEGF-A is also essential for the induction of endothelial tip cells, but it is not known how single tip cells are selected to lead each vessel sprout, and how tip-cell numbers are determined. Here we present evidence that delta-like 4 (Dll4)–Notch1 signalling regulates the formation of appropriate numbers of tip cells to… 

A study of Notch signalling in developmental angiogenesis

The studies show that Notch signalling regulates endothelial tip cell formation and vessel stability to fine-tune vessel patterning and demonstrate that Nrarp provides a molecular link to Wnt signalling to regulate vessel stability.

Development: Notch mediates the sprouting of tip cells

Whereas VEGFA promotes the sprouting of tip cells, Notch–Dll4 signalling dampens responsiveness to VEG FA in some cells but not in others, thereby mediating tip-cell selection.

Dll4 and Notch signalling couples sprouting angiogenesis and artery formation

Genetic experiments in postnatal mice show that the level of active Notch signalling is more important than the direct Dll4-mediated cell–cell communication between endothelial cells in controlling Notch-dependent vessel growth.

Development: Notch mediates the sprouting of tip cells

Whereas V EGF promotes the sprouting of tip cells, Notch–Dll4 signalling dampens responsiveness to VEGF in some cells but not in others, thereby mediating tip-cell selection, which could mean that inhibitors and modulators of this Notch-Dll 4 pathway might prove to be useful for the treatment of pathological angiogenesis in tumours.

Extrinsic Notch Ligand Delta-Like 1 Regulates Tip Cell Selection and Vascular Branching Morphogenesis

Dll1 acts as an extrinsic cue involved in tip cell selection, which directs vessel sprouting and branch formation in the mouse retina.

Retinal myeloid cells regulate tip cell selection and vascular branching morphogenesis via Notch ligand Delta-like 1

It is shown, using genetic reporter and conditional deletion strategies, that myeloid cells regulate tip cell numbers and Dll4 expression via the Notch ligand Dll1 during vascular development in the retina during angiogenesis.

Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo

Genetic evidence is presented that flt1 (vegfr1) acts, in a Notch-dependent manner, as a negative regulator of tip cell formation and sprout guidance in the trunk vasculature of zebrafish embryos.

Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor.

It is indicated that the Notch pathway controls lymphatic endothelial quiescence, and explain why LECs are poorly responsive to VEGF compared with V EGF-C.

Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis

It is suggested that blocking ephrin-B2 reverse signalling may be an attractive alternative or combinatorial anti-angiogenic therapy strategy to disrupt VEGFR2 function in tumour angiogenesis.
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