1. by Donna Nichol, and Heidi Stuhlmann
EGFL7: a unique angiogenic signaling factor in vascular development and disease
by Donna Nichol, and Heidi Stuhlmann
Blood
Volume 119(6):
February 9, 2012
©2012 by American Society of Hematology

2. Gene structure and protein organization of Egfl7.
Gene structure and protein organization of Egfl7. (A) The Egfl7 gene consists of 11 exons and a miRNA, miR126, embedded in the intronic region located downstream of exon 7. The protein is encoded in exons 3-10 (red boxes). (B) The EGFL7 protein sequence contains several putative protein domains, including a signal peptide (blue box), an EMI domain (yellow box), an EGF domain that contains a Delta-Serrate-LAG-2 (DSL) motif (orange box), and a Ca2+ binding EGF domain (red box).
Donna Nichol, and Heidi Stuhlmann Blood 2012;119:
©2012 by American Society of Hematology

3. Model depicting the role of EGFL7 in angiogenesis and stem cell behavior.
Model depicting the role of EGFL7 in angiogenesis and stem cell behavior. (A-B) EGFL7 is a secreted protein that is expressed by endothelial cells, including the stalk and tip cells of sprouting vessels. Once secreted, EGFL7 binds to the ECM and shows overlapping expression with fibronectin and collagen type IV. (A) EGFL7 controls endothelial cell sprouting, migration, and proliferation. (B). EGFL7 also signals to the ECM and modulates its rigidity by inhibiting lysyl oxidase (LOX)–mediated conversion of tropoelastin into elastin. (C) EGFL7 promotes embryonic stem cell proliferation and inhibits proliferation of adult neuronal stem cells.
Donna Nichol, and Heidi Stuhlmann Blood 2012;119:
©2012 by American Society of Hematology

4. Model describing the putative role of EGFL7 in Notch signaling in different vascular beds.
Model describing the putative role of EGFL7 in Notch signaling in different vascular beds. (A) EGFL7 signaling in the postnatal retina. EGFL7 antagonizes Notch/ligand interaction by either binding to the receptor or its corresponding ligand and inhibits target gene expression. (B) EGFL7 signaling in the embryo. EGFL7 indirectly enhances DLL4/Notch signaling by binding to Jagged1, preventing an interaction with the glycosylated Notch receptor, and promoting DLL4 interaction with Notch. ECD indicates extracellular domain; and NICD, Notch intracellular domain.
Donna Nichol, and Heidi Stuhlmann Blood 2012;119:
©2012 by American Society of Hematology