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.
Mesh Terms:
Animals, Cell Differentiation, Cell Line, Cell Proliferation, Cells, Cultured, Endothelial Growth Factors, Humans, Mice, Neurons, Protein Binding, Receptors, Notch, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Stem Cells, Two-Hybrid System Techniques
Animals, Cell Differentiation, Cell Line, Cell Proliferation, Cells, Cultured, Endothelial Growth Factors, Humans, Mice, Neurons, Protein Binding, Receptors, Notch, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Stem Cells, Two-Hybrid System Techniques
Nat. Cell Biol.
Date: Jul. 01, 2009
PubMed ID: 19503073
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