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EGFL7 regulates vascular remodeling in vivo
Author(s) -
Nichol Donna,
Durrans Anna,
Bambino Kathryn,
Fitch Mike,
Stuhlmann Heidi
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.312.1
Subject(s) - biology , microbiology and biotechnology , extracellular matrix , transgene , yolk sac , genetically modified mouse , endothelium , in vivo , angiogenesis , vascular smooth muscle , vascular endothelial growth factor b , mural cell , anatomy , embryo , endocrinology , gene , vascular endothelial growth factor a , cancer research , vascular endothelial growth factor , genetics , smooth muscle , vegf receptors
Egfl7 encodes a secreted protein that is part of the interstitial extracellular matrix. Its embryonic expression is restricted to the sites of mesodermal precursors of angioblasts, the vascular endothelium in the embryo proper and the yolk sac. In mice that lack E gfl 7, 50% die in utero of unknown causes. Because loss‐of‐function studies have not provided a clear role for this factor, we generated EGFL7 transgenic mice to elucidate its function in vivo. In these mice, EGFL7 is overexpressed in endothelial and hematopoietic cells, under the control of the Tie2 promoter. EGFL7 transgenics are both viable and fertile; however, at E12.5 they show hemorrhaging and vascular remodeling defects, which are accompanied by a lower than expected Mendalian ratio. At E10.5, EGFL7 transgenics exhibit vessel fusion and aberrant endothelial cell clusters in the head vasculature that is not apparent in wild types. At E12.5, transgenics show enlarged vessel lumen and an impairment in vascular smooth muscle cell recruitment. Remodeling defects are also evident in other vascular beds. 20% of E12.5 yolk sacs show similar defects to those observed in the head. Likewise, post‐natal transgenic retinal vasculature exhibits remodeling defects and an increase in vascular coverage. Together, our gain‐of‐function studies show that EGFL7 controls vascular remodeling in several vascular beds in vivo, uncovering a novel role for EGFL7.