title: Epidermal growth factor-like domain 7 is a marker of the endothelial lineage and active angiogenesis.
abstract: Epidermal growth factor-like domain 7 (Egfl7) expression in the developing embryo is largely restricted to sites of mesodermal progenitors of angioblasts/hemangioblasts and the vascular endothelium. We hypothesize that Egfl7 marks the endothelial lineage during embryonic development, and can be used to define the emergence of endothelial progenitor cells, as well as to visualize newly-forming vasculature in the embryo and during the processes of physiologic and pathologic angiogenesis in the adult. We have generated a transgenic mouse strain that expresses enhanced green fluorescent protein (eGFP) under the control of a minimal Egfl7 regulatory sequence (Egfl7:eGFP). Expression of the transgene recapitulated that of endogenous Egfl7 at sites of vasculogenesis and angiogenesis in the allantois, yolk sac, and in the embryo proper. The transgene was not expressed in the quiescent endothelium of most adult organs. However, the uterus and ovary, which undergo vascular growth and remodeling throughout the estrus cycle, expressed high levels of Egfl7:eGFP. Importantly, expression of the Egfl7:eGFP transgene was induced in adult neovasculature. We also found that increased Egfl7 expression contributed to pathologic revascularization in the mouse retina. To our knowledge, this is the first mouse model that enables monitoring of endothelial cells at sites of active vasculogenesis and angiogenesis. This model also facilitated the isolation and characterization of EGFL7(+) endothelial cell populations by fluorescence activated cell sorting (FACS). Together, our results demonstrate that the Egfl7:eGFP reporter mouse is a valuable tool that can be used to elucidate the mechanisms by which blood vessels form during development and under pathologic circumstances.
authors.affiliation: Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York; Department of Cell and Developmental Biology, Weill Cornell Graduate School of Medical Sciences, Program in Biochemistry and Structural Biology, Cell and Developmental Biology, and Molecular Biology, New York, New York.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Bambino
authors.forename: Lauretta A
authors.initials: LA
authors.lastname: Lacko
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hajjar
authors.forename: Heidi
authors.initials: H
authors.lastname: Stuhlmann
mesh_terms: D000482:Allantois / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins; D019070:Cell Lineage; D066255:EGF Family of Proteins; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D051379:Mice; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D010053:Ovary / Q000254:growth & development / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000378:metabolism; D014599:Uterus / Q000254:growth & development / Q000378:metabolism; D015017:Yolk Sac / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C479627:Egfl7 protein, mouse; D011506:Proteins
keywords: eGFP; endothelial reporter; transgenic mice; vascular development
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