Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal

被引：123

作者：

Schmidt, Mirko H. H. ^{[1
,2
]}

Bicker, Frank ^{[2
]}

Nikolic, Iva ^{[2
]}

Meister, Jeannette ^{[2
]}

Babuke, Tanja ^{[1
]}

Picuric, Srdjan ^{[1
]}

Mueller-Esterl, Werner ^{[1
]}

Plate, Karl H. ^{[2
]}

Dikic, Ivan ^{[1
]}

机构：

[1] Goethe Univ Frankfurt, Sch Med, Inst Biochem 2, D-60590 Frankfurt, Germany

[2] Goethe Univ Frankfurt, Sch Med, Inst Neurol, D-60528 Frankfurt, Germany

来源：

NATURE CELL BIOLOGY | 2009年 / 11卷 / 07期

关键词：

NUCLEAR ANTIGEN-2; MAMMALIAN NOTCH; IN-VIVO; DROSOPHILA; RECEPTOR; DELTA; GENE; ACTIVATION; SERRATE; PATHWAY;

D O I：

10.1038/ncb1896

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：873 / U245

页数：24

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