Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis

Tang Long Shen, Ann Y J Park, Ana Alcaraz, Xu Peng, Ihnkyung Jang, Pandelakis Koni, Richard A. Flavell, Hua Gu, Jun Lin Guan

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)941-952
Number of pages12
JournalJournal of Cell Biology
Volume169
Issue number6
DOIs
StatePublished - Jun 1 2005

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Focal Adhesion Protein-Tyrosine Kinases
Embryonic Development
Blood Vessels
Endothelial Cells
Embryonic Structures
Phenotype
Yolk Sac
Growth Factor Receptors
Integrins
Placenta
Cell Movement
Signal Transduction
Edema
Cell Survival
Cell Proliferation
Hemorrhage

ASJC Scopus subject areas

  • Cell Biology

Cite this

Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. / Shen, Tang Long; Park, Ann Y J; Alcaraz, Ana; Peng, Xu; Jang, Ihnkyung; Koni, Pandelakis; Flavell, Richard A.; Gu, Hua; Guan, Jun Lin.

In: Journal of Cell Biology, Vol. 169, No. 6, 01.06.2005, p. 941-952.

Research output: Contribution to journalArticle

Shen, Tang Long ; Park, Ann Y J ; Alcaraz, Ana ; Peng, Xu ; Jang, Ihnkyung ; Koni, Pandelakis ; Flavell, Richard A. ; Gu, Hua ; Guan, Jun Lin. / Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. In: Journal of Cell Biology. 2005 ; Vol. 169, No. 6. pp. 941-952.
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