Endothelial RAF1/ERK activation regulates arterial morphogenesis

Deng, Yong; Larrivée, Bruno; Zhuang, Zhen W.; Atri, Deepak; Moraes, Filipa; Prahst, Claudia; Eichmann, Anne; Simons, Michael

doi:10.1182/blood-2012-12-474601

Cited by 61 publications

(52 citation statements)

References 45 publications

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“…ERK pathway has been reported to function during the artery-vein specification and arterial morphogenesis 21,35 . The EHT process was inhibited in both erk2 MO and erk2 mRNA-injected embryos ( Supplementary Fig.…”

Section: Article Nature Communications | Doi: 101038/ncomms4431mentioning

confidence: 99%

Inhibition of endothelial ERK signalling by Smad1/5 is essential for haematopoietic stem cell emergence

Zhang

et al. 2014

Nat Commun

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The earliest HSCs are derived from haemogenic endothelium via endothelial-to-haematopoietic transition during vertebrate embryogenesis; however, the underlying mechanism is largely unclear. Here we show that interplay of Smad1/5 and ERK signalling is essential for haemogenic endothelium-based HSC emergence. Smad1/5 directly inhibits erk expression through recruiting HDAC1 to and inducing de-acetylation of the erk promoter in endothelial cells. Over-activated ERK signalling conferred by inhibition of Smad1/5 promotes the arterial endothelial cell fate and constitutively strengthens the tight junction between endothelial cells, thereby repressing the specification of haemogenic endothelium and the following endothelial-to-haematopoietic transition process. These findings provide new insights into the in vitro generation of transplantable HSCs for potential clinical applications.

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Section: Article Nature Communications | Doi: 101038/ncomms4431mentioning

confidence: 99%

Inhibition of endothelial ERK signalling by Smad1/5 is essential for haematopoietic stem cell emergence

Zhang

et al. 2014

Nat Commun

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“…[21][22][23][24] It was found that a strong stimulation of the ERK pathway directs endothelial differentiation to the arterial phenotype while activation of PI3K/AKT/Akt pathway inhibits arteriogenesis in favor of venous differentiation. Moreover, Deng et al 21 …”

Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Signaling Pathways in the Specification of Arteries and Veins

Corada

Morini

Dejana

2014

ATVB

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Abstract-The establishment of arterial and venous identity of endothelial cells is critical for the proper anatomic configuration and function of the vascular tree. Arterial and venous specification of endothelial cells is determined by genetic factors, although surrounding cells and hemodynamic forces may also contribute to vascular remodeling. This review provides an overview of the signaling pathways and related transcription factors implicated in differentiation of endothelial cells. We will discuss, in particular, the role of upstream and downstream effectors of Wnt, Sox, and Notch pathways.

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“…One of the major mechanisms to translate such extracellular inputs into a cellular response is protein and lipid phosphorylation. However, specific roles for regulation of phosphorylation during angiogenesis have been assigned to only a few kinases and phosphatases (Deng et al, 2013;Nakayama et al, 2013;Serra et al, 2015;Yoshioka et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner

et al. 2016

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cAMP-dependent protein kinase A (PKA) is a ubiquitously expressed serine/threonine kinase that regulates a variety of cellular functions. Here, we demonstrate that endothelial PKA activity is essential for vascular development, specifically regulating the transition from sprouting to stabilization of nascent vessels. Inhibition of endothelial PKA by endothelial cell-specific expression of dominant-negative PKA in mice led to perturbed vascular development, hemorrhage and embryonic lethality at mid-gestation. During perinatal retinal angiogenesis, inhibition of PKA resulted in hypersprouting as a result of increased numbers of tip cells. In zebrafish, cell autonomous PKA inhibition also increased and sustained endothelial cell motility, driving cells to become tip cells. Although these effects of PKA inhibition were highly reminiscent of Notch inhibition effects, our data demonstrate that PKA and Notch independently regulate tip and stalk cell formation and behavior.

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Endothelial RAF1/ERK activation regulates arterial morphogenesis

Abstract: Key Points RAF1 Ser259 phosphorylation is a critical regulator step controlling arterial morphogenesis and arterial-venous patterning. ERK activation controls DLL4/Notch signaling and semaphorin 6A–mediated endothelial cell repulsion.

Cited by 61 publications

References 45 publications

Inhibition of endothelial ERK signalling by Smad1/5 is essential for haematopoietic stem cell emergence

Inhibition of endothelial ERK signalling by Smad1/5 is essential for haematopoietic stem cell emergence

Signaling Pathways in the Specification of Arteries and Veins

cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner

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