Dll4 and Notch signalling couples sprouting angiogenesis and artery formation.
Mara E PitulescuInga SchmidtBenedetto Daniele GiaimoTobiah AntoineFrank BerkenfeldFrancesca FerranteHongryeol ParkManuel EhlingDaniel BiljesSusana F RochaUrs H LangenMartin StehlingTakashi NagasawaNapoleone FerraraTilman BorggrefeRalf H AdamsPublished in: Nature cell biology (2017)
Endothelial sprouting and proliferation are tightly coordinated processes mediating the formation of new blood vessels during physiological and pathological angiogenesis. Endothelial tip cells lead sprouts and are thought to suppress tip-like behaviour in adjacent stalk endothelial cells by activating Notch. Here, we show with genetic experiments in postnatal mice that the level of active Notch signalling is more important than the direct Dll4-mediated cell-cell communication between endothelial cells. We identify endothelial expression of VEGF-A and of the chemokine receptor CXCR4 as key processes controlling Notch-dependent vessel growth. Surprisingly, genetic experiments targeting endothelial tip cells in vivo reveal that they retain their function without Dll4 and are also not replaced by adjacent, Dll4-positive cells. Instead, activation of Notch directs tip-derived endothelial cells into developing arteries and thereby establishes that Dll4-Notch signalling couples sprouting angiogenesis and artery formation.
Keyphrases
- endothelial cells
- induced apoptosis
- high glucose
- vascular endothelial growth factor
- cell proliferation
- cell cycle arrest
- signaling pathway
- single cell
- genome wide
- endoplasmic reticulum stress
- type diabetes
- cell death
- stem cells
- cell therapy
- poor prognosis
- gene expression
- preterm infants
- dna methylation
- oxidative stress
- long non coding rna
- wound healing
- bone marrow
- skeletal muscle
- insulin resistance
- cell migration