title: Roles of cyclic adenosine monophosphate signaling in endothelial cell differentiation and arterial-venous specification during vascular development.
abstract: Cyclic adenosine monophosphate (cAMP) is an important second messenger mediating physiological functions, including metabolism, gene expression, cell growth and differentiation. Recently, we demonstrated novel roles of cAMP pathway in endothelial cell (EC) differentiation and arterial-venous specification using an embryonic stem cell differentiation system. These studies offered a concept that vascular formation is accomplished by a 2-layered mechanism: (1) a basal mechanism for common EC differentiation, whereby vascular endothelial growth factor (VEGF) signaling plays a central role in the basal mechanism, and (2) a vascular diversification mechanism working on the basis of common EC differentiation. Vascular diversification, such as artery and vein formation, can be only achieved by enacting specific machineries in the presence of the basal EC machinery. cAMP/protein kinase A signaling contributes to common EC differentiation through upregulation of the VEGF-A receptors, Flk1 and neuropilin1. On the other hand, cAMP can activate phosphatidylinositol-3 kinase, which induces an arterial fate in vascular progenitors via dual activation of Notch and β-catenin signaling as an arterial-specific machinery. cAMP signaling thus plays a pivotal role in both the basal and diversification machinery during vascular development.
authors.affiliation: Department of Cell Growth and Differentiation, Kyoto University, Kyoto 606-8507, Japan. yamamizu@frontier.kyoto-u.ac.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamamizu
authors.forename: Jun K
authors.initials: JK
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D001158:Arteries / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D036342:Ephrins / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D008322:Mammals; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis / Q000235:genetics; D015290:Second Messenger Systems / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics; D014680:Veins / Q000196:embryology*; D015027:Zebrafish; D051176:beta Catenin / Q000502:physiology
chemical_list: D036342:Ephrins; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D017868:Cyclic AMP-Dependent Protein Kinases