Schmidt Mirko H H, Bicker Frank, Nikolic Iva, Meister Jeannette, Babuke Tanja, Picuric Srdjan, Müller-Esterl Werner, Plate Karl H, Dikic Ivan
Institute of Biochemistry II, Johann Wolfgang Goethe University School of Medicine, Frankfurt am Main, Germany.
Nat Cell Biol. 2009 Jul;11(7):873-80. doi: 10.1038/ncb1896. Epub 2009 Jun 7.
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.
表皮生长因子样结构域7（EGFL7）是一种分泌因子，参与细胞迁移和血管形成等细胞反应；然而，EGFL7作用的分子机制在很大程度上尚不清楚。在这里，我们确定了Notch家族的跨膜受体为EGFL7结合分子。分泌的EGFL7与Notch中参与配体介导的受体激活的区域结合，从而作为Notch信号的拮抗剂。体外神经干细胞（NSC）中EGFL7的表达降低了Notch特异性信号，因此，减少了NSC的增殖和自我更新。这种改变的Notch信号导致培养的NSC的分化模式向过多的神经元和少突胶质细胞转变。我们确定神经元是大脑中EGFL7的来源，这表明脑源性EGFL7作为Notch信号的内源性拮抗剂，调节来自脑室下区的成年NSC的增殖和分化。
