Peripheral Nerve-derived CXCL12 and VEGF-A Regulate the Patterning of Arterial Vessel Branching in Developing Limb Skin

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2013 Feb 12

PMID 23395391

Citations 76

Authors

Wenling Li

Hiroshi Kohara

Yutaka Uchida

Jennifer M James

Kosha Soneji

Darran G Cronshaw

Yong-Rui Zou

Takashi Nagasawa

Yoh-Suke Mukouyama

Affiliations

Soon will be listed here.

Abstract

In developing limb skin, peripheral nerves provide a spatial template that controls the branching pattern and differentiation of arteries. Our previous studies indicate that nerve-derived VEGF-A is required for arterial differentiation but not for nerve-vessel alignment. In this study, we demonstrate that nerve-vessel alignment depends on the activity of Cxcl12-Cxcr4 chemokine signaling. Genetic inactivation of Cxcl12-Cxcr4 signaling perturbs nerve-vessel alignment and abolishes arteriogenesis. Further in vitro assays allow us to uncouple nerve-vessel alignment and arteriogenesis, revealing that nerve-derived Cxcl12 stimulates endothelial cell migration, whereas nerve-derived VEGF-A is responsible for arterial differentiation. These findings suggest a coordinated sequential action in which nerve Cxcl12 functions over a distance to recruit vessels to align with nerves, and subsequent arterial differentiation presumably requires a local action of nerve VEGF-A in the nerve-associated vessels.

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