title: Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis.
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.
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Tang-Long
authors.initials: TL
authors.lastname: Shen
authors.forename: Ann Y-J
authors.initials: AY
authors.lastname: Park
authors.forename: Ana
authors.initials: A
authors.lastname: Alcaraz
authors.forename: Xu
authors.initials: X
authors.lastname: Peng
authors.forename: Ihnkyung
authors.initials: I
authors.lastname: Jang
authors.forename: Pandelakis
authors.initials: P
authors.lastname: Koni
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Hua
authors.initials: H
authors.lastname: Gu
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D002196:Capillaries / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005804:Genes, Lethal / Q000502:physiology; D006470:Hemorrhage / Q000235:genetics / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D051419:Paxillin; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010920:Placenta / Q000002:abnormalities / Q000098:blood supply; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D003598:Cytoskeletal Proteins; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse