Signaling Pathways in the Specification of Arteries and Veins

Corada, Monica; Morini, Marco; Dejana, Elisabetta

doi:10.1161/atvbaha.114.303218

Cited by 89 publications

(74 citation statements)

References 67 publications

(74 reference statements)

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“…Notch pathway genes are highly expressed by arterial ECs, which are exposed to higher flow rates and shear stress, whereas venous expression is low or undetectable5859. This is consistent with numerous studies reporting Notch activation in blood vessel ECs in response to flow and laminar shear stress606162.…”

Section: Discussionsupporting

confidence: 89%

Blood flow controls bone vascular function and osteogenesis

et al. 2016

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While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system.

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Section: Discussionsupporting

confidence: 89%

Blood flow controls bone vascular function and osteogenesis

et al. 2016

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“…Molecular mechanisms that control the induction of arterial and venous endothelial identity include upstream and downstream effectors of Wnt, Sox, and Notch pathways, 1 but little is known on the determinants that maintain this specific identity of the endothelium. van Geemen et al 2 bring convincing evidence that in vivo endothelial phenotype of human arteries and veins is determined by F-actin-anchored focal adhesion and biomechanical properties of extracellular matrix.…”

Section: Endothelial Phenotypementioning

confidence: 99%

Endothelium

Boulanger

2016

ATVB

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“…Likewise, inhibition of Nrg1-ErbB signaling in zebrafish embryos completely blocks trabeculation Peshkovsky et al, 2011;Samsa et al, 2013;Staudt et al, 2014). Notch ligands and receptors are expressed in endocardial cells during development, and Notch signaling regulates many aspects of endothelial biology, including artery-vein specification, angiogenesis and proliferation (Benedito and Hellstrom, 2013;Corada et al, 2014;de la Pompa and Epstein, 2012;Gridley, 2010). Upon ligand binding, the cleaved Notch receptor intracellular domain (NICD) translocates to the nucleus, where it acts as a co-factor to promote transcription of Notch effectors, including ephrin B2, an essential upstream regulator of Nrg1 signaling (Grego-Bessa et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Cardiac contraction activates endocardial Notch signaling to modulate chamber maturation in zebrafish

et al. 2015

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Congenital heart disease often features structural abnormalities that emerge during development. Accumulating evidence indicates a crucial role for cardiac contraction and the resulting fluid forces in shaping the heart, yet the molecular basis of this function is largely unknown. Using the zebrafish as a model of early heart development, we investigated the role of cardiac contraction in chamber maturation, focusing on the formation of muscular protrusions called trabeculae. By genetic and pharmacological ablation of cardiac contraction, we showed that cardiac contraction is required for trabeculation through its role in regulating notch1b transcription in the ventricular endocardium. We also showed that Notch1 activation induces expression of ephrin b2a (efnb2a) and neuregulin 1 (nrg1) in the endocardium to promote trabeculation and that forced Notch activation in the absence of cardiac contraction rescues efnb2a and nrg1 expression. Using in vitro and in vivo systems, we showed that primary cilia are important mediators of fluid flow to stimulate Notch expression. Together, our findings describe an essential role for cardiac contraction-responsive transcriptional changes in endocardial cells to regulate cardiac chamber maturation.

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Signaling Pathways in the Specification of Arteries and Veins

Cited by 89 publications

References 67 publications

Blood flow controls bone vascular function and osteogenesis

Blood flow controls bone vascular function and osteogenesis

Endothelium

Cardiac contraction activates endocardial Notch signaling to modulate chamber maturation in zebrafish

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