title: Dosage-dependent requirement for mouse Vezf1 in vascular system development.
abstract: Vezf1 is an early development gene that encodes a zinc finger transcription factor. In the developing embryo, Vezf1 is expressed in the yolk sac mesoderm and the endothelium of the developing vasculature and, in addition, in mesodermal and neuronal tissues. Targeted inactivation of Vezf1 in mice reveals that it acts in a closely regulated, dose-dependent fashion on the development of the blood vascular and lymphatic system. Homozygous mutant embryos display vascular remodeling defects and loss of vascular integrity leading to localized hemorrhaging. Ultrastructural analysis shows defective endothelial cell adhesion and tight junction formation in the mutant vessels. Moreover, in heterozygous embryos, haploinsufficiency is observed that is characterized by lymphatic hypervascularization associated with hemorrhaging and edema in the jugular region; a phenotype reminiscent of the human congenital lymphatic malformation syndrome cystic hygroma.
authors.affiliation: Department of Cell Biology, Division of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Kuhnert
authors.forename: Luisa
authors.initials: L
authors.lastname: Campagnolo
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Xiong
authors.forename: Derek
authors.initials: D
authors.lastname: Lemons
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fitch
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zou
authors.forename: William B
authors.initials: WB
authors.lastname: Kiosses
authors.forename: Humphrey
authors.initials: H
authors.lastname: Gardner
authors.forename: Heidi
authors.initials: H
authors.lastname: Stuhlmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000002:abnormalities / Q000196:embryology*; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins; D047108:Embryonic Development; D004730:Endothelium, Vascular / Q000002:abnormalities / Q000196:embryology; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D051741:Kruppel-Like Transcription Factors; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*; D015017:Yolk Sac / Q000502:physiology
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C117684:Vezf1 protein, mouse