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(Circulation Research. 2008;103:573.)
© 2008 American Heart Association, Inc.

Review

Role of Crosstalk Between Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathways in Artery–Vein Specification

Charles C. Hong, Tsutomu Kume, Randall T. Peterson

From the Division of Cardiovascular Medicine (C.C.H., T.K.), Department of Medicine; and Departments of Pharmacology (C.C.H.) and Cell and Developmental Biology (T.K.), Vanderbilt University School of Medicine, Nashville, Tenn; and Cardiovascular Research Center and Division of Cardiology (R.T.P.), Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass.

Correspondence to Charles C. Hong, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, 383 PRB, 2220 Pierce Ave, Nashville, TN 37232. E-mail charles.c.hong{at}vanderbilt.edu

This Review is part of a thematic series on Arterial Specification: A Finishing School for the Endothelium, which includes the following articles:

Role of Crosstalk Between Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated

Kinase/Mitogen-Activated Protein Kinase Pathways in Artery–Vein Specification

Brothers and Sisters: Molecular Insights into Arterial–Venous Heterogeneity

Molecular Mechanisms of Branching Morphogenesis

Fibroblast Growth Factor–Hedgehog Signaling in Coronary Arterial Circulation

Arterial Guidance

Arterial–Venous Specification in Development
Michael Simons Guest Editor

Functional and structural differences between arteries and veins lie at the core of the circulatory system, both in health and disease. Therefore, understanding how artery and vein cell identities are established is a fundamental biological challenge with significant clinical implications. Molecular genetic studies in zebrafish and other vertebrates in the past decade have begun to reveal in detail the complex network of molecular pathways that specify artery and vein cell fates during embryonic development. Recently, a chemical genetic approach has revealed evidence that artery–vein specification is governed by cross talk between phosphoinositide 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in artery–vein specification. We discuss recent findings on the signaling pathways involved in artery–vein specification during zebrafish development and compare and contrast these results to those from mammalian systems. It is anticipated that the complementary approaches of genetics and chemical biology, involving a variety of model organisms and systems, will lead to a better understanding of artery–vein specification and possibly to novel therapeutic approaches to treat vascular diseases.

Key Words: artery–vein specification • signaling crosstalk • Shh • VEGF • Notch • Fox