Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal.
Epidermal growth factor-like domain 7 (EGFL7) is a secreted factor implicated in cellular responses such as cell migration and blood vessel formation; however the molecular mechanisms underlying the effects of EGFL7 are largely unknown. Here we have identified transmembrane receptors of the Notch family as EGFL7-binding molecules. Secreted EGFL7 binds to a region in Notch involved in ligand-mediated receptor activation, thus acting as an antagonist of Notch signalling. Expression of EGFL7 in neural stem cells (NSCs) in vitro decreased Notch-specific signalling and consequently, reduced proliferation and self-renewal of NSCs. Such altered Notch signalling caused a shift in the differentiation pattern of cultured NSCs towards an excess of neurons and oligodendrocytes. We identified neurons as a source of EGFL7 in the brain, suggesting that brain-derived EGFL7 acts as an endogenous antagonist of Notch signalling that regulates proliferation and differentiation of subventricular zone-derived adult NSCs.
Schmidt
Mirko H H
MHH
Institute of Biochemistry II, Johann Wolfgang Goethe University School of Medicine, Frankfurt am Main, Germany. Mirko.Schmidt@kgu.de
Bicker
Frank
F
Nikolic
Iva
I
Meister
Jeannette
J
Babuke
Tanja
T
Picuric
Srdjan
S
Müller-Esterl
Werner
W
Plate
Karl H
KH
Dikic
Ivan
I
D000818:Animals; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; D016228:Endothelial Growth Factors; D051880:Receptors, Notch