MAPping out arteries and veins.
Growing evidence suggests that a genetic program specifies the identity of arteries and veins before the onset of circulation. A signaling cascade involving sonic hedgehog (Shh), vascular endothelial growth factor (VEGF), the VEGF receptor 2 (VEGFR2), homeobox proteins Foxc1 and Foxc2, the Notch receptor, and the downstream transcription factor gridlock is required for expression of arterial markers, whereas only a single transcription factor, COUP-TFII (chicken ovalbumin upstream promoter-transcription factor II), has previously been implicated in maintaining venous fate. Recent work has now implicated two competing pathways downstream of VEGFR2 in arterial versus venous specification: Activation of the phospholipase C-gamma (PLC-gamma)-mitogen-activated protein kinase (MAPK) pathway acts in arterial specification, whereas the phosphoinositide 3-kinase (PI3K)-Akt pathway acts to allow a venous fate by inhibition of the PLC-gamma-MAPK pathway. Here, we review this work and discuss how activation of the MAPK signaling cascade could stimulate an arterial fate.
Lamont
Ryan E
RE
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary AB, Canada T2N 4N1, Canada. relamont@ucalgary.ca
Childs
Sarah
S
D000818:Animals; D030801:Animals, Genetically Modified; D001158:Arteries / Q000196:embryology*; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D051837:COUP Transcription Factor II / Q000502:physiology; D036342:Ephrins / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D009024:Morphogenesis / Q000235:genetics; D009928:Organ Specificity; D051880:Receptors, Notch / Q000502:physiology; D019170:Somites / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000172:deficiency / Q000502:physiology; D014680:Veins / Q000201:enzymology*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D051837:COUP Transcription Factor II; D036342:Ephrins; D053823:Hedgehog Proteins; D051880:Receptors, Notch; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D029961:Zebrafish Proteins; C465570:Shh protein, mouse; C405954:hey2 protein, zebrafish; C467480:vascular endothelial growth factor A, mouse