Conditional Knockout of Focal Adhesion Kinase in Endothelial Cells Reveals Its Role in Angiogenesis and Vascular Development in Late Embryogenesis

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2005 Jun 22

PMID 15967814

Citations 156

Authors

Tang-Long Shen

Ann Y-J Park

Ana Alcaraz

Xu Peng

Ihnkyung Jang

Pandelakis Koni

Richard A Flavell

Hua Gu

Jun-Lin Guan

Affiliations

Soon will be listed here.

Abstract

Focal adhesion kinase (FAK) is a critical mediator of signal transduction by integrins and growth factor receptors in a variety of cells including endothelial cells (ECs). Here, we describe EC-specific knockout of FAK using a Cre-loxP approach. In contrast to the total FAK knockout, deletion of FAK specifically in ECs did not affect early embryonic development including normal vasculogenesis. However, in late embryogenesis, FAK deletion in the ECs led to defective angiogenesis in the embryos, yolk sac, and placenta, impaired vasculature and associated hemorrhage, edema, and developmental delay, and late embryonic lethal phenotype. Histologically, ECs and blood vessels in the mutant embryos present a disorganized, detached, and apoptotic appearance. Consistent with these phenotypes, deletion of FAK in ECs isolated from the floxed FAK mice led to reduced tubulogenesis, cell survival, proliferation, and migration in vitro. Together, these results strongly suggest a role of FAK in angiogenesis and vascular development due to its essential function in the regulation of multiple EC activities.

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