The role of Egfl7 in vascular morphogenesis.
EGFL7 was identified by a number of groups as a putative secreted factor produced by the vascular endothelial cells (ECs). In a recent publication, we showed that EGFL7 regulates midline angioblast migration in zebrafish embryos-a key step in vascular tubulogenesis. In this study, we further characterized the zebrafish vasculature in the Egfl7 knockdown embryos at the ultrastructural level, and found that malformation of axial vessels is indeed due to the accumulation of angioblasts and aberrant connection among themselves, but not abnormal interaction between ECs and other cell types. Using in vitro biochemical assays, we demonstrated that EGFL7 is tightly associated with the extracellular matrix (ECM), and it supports EC migration either as a single factor or in combination with other ECM molecules. In order to evaluate if the biological function of EGFL7 is evolutionarily conserved, we generated Egfl7 knockout mice and analysed vascular development in a number of tissues. We found that vascular coverage of a given tissue is reduced or delayed, and vascular morphogenesis is defective in the Egfl7 mutant mice. Taken together, we conclude that EGFL7 provides a proper microenvironment for endothelial cell migration, thereby enabling accurate patterning. Our study indicates that the molecular composition of the ECM influences vascular morphogenesis.
Schmidt
Maike
M
Tumor Biology and Angiogenesis Department, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
De Mazière
Ann
A
Smyczek
Tanya
T
Gray
Alane
A
Parker
Leon
L
Filvaroff
Ellen
E
French
Dorothy
D
van Dijk
Suzanne
S
Klumperman
Judith
J
Ye
Weilan
W
D000818:Animals; D001808:Blood Vessels / Q000196:embryology* / Q000648:ultrastructure; D019521:Body Patterning; D002465:Cell Movement; D004622:Embryo, Mammalian / Q000098:blood supply* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000648:ultrastructure; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D009369:Neoplasms / Q000098:blood supply; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
C484962:Egfl7 protein, zebrafish; D016326:Extracellular Matrix Proteins; D029961:Zebrafish Proteins