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(Circulation Research. 2008;103:784.)
© 2008 American Heart Association, Inc.

Review

Branching Morphogenesis

Arie Horowitz, Michael Simons

From the Angiogenesis Research Center and Section of Cardiology (A.H.), Dartmouth Medical School, Lebanon, NH; and Section of Cardiovascular Medicine (M.S.), Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn.

Correspondence to Arie Horowitz, PhD, Angiogenesis Research Center, Dartmouth Medical School, One Medical Center Dr, Borwell 554W, Lebanon, NH 03756. E-mail arie.horowitz{at}dartmouth.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

Branching Morphogenesis

Brothers and Sisters: Molecular Insights into Arterial–Venous Heterogeneity

Fibroblast Growth Factor–Hedgehog Signaling in Coronary Arterial Circulation

Arterial Guidance

Arterial–Venous Specification in Development
Michael Simons Guest Editor

Tubular structures are a fundamental anatomic theme recurring in a wide range of animal species. In mammals, tubulogenesis underscores the development of several systems and organs, including the vascular system, the lungs, and the kidneys. All tubular systems are hierarchical, branching into segments of gradually diminishing diameter. There are only 2 cell types that form the lumen of tubular systems: either endothelial cells in the vascular system or epithelial cells in all other organs. The most important feature in determining the morphology of the tubular systems is the frequency and geometry of branching. Hence, deciphering the molecular mechanisms underlying the sprouting of new branches from preexisting ones is the key to understanding the formation of tubular systems. The morphological similarity between the various tubular systems is underscored by similarities between the signaling pathways which control their branching. A prominent feature common to these pathways is their duality—an agonist counterbalanced by an inhibitor. The formation of the tracheal system in Drosophila melanogaster is driven by fibroblast growth factor and inhibited by Sprouty/Notch. In vertebrates, the analogous pathways are fibroblast growth factor and transforming growth factor-β in epithelial tubular systems or vascular endothelial growth factor and Notch in the vascular system.

Key Words: branching • tubulogenesis • vascular system • tracheal system • ureteric system

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