Letter abstract

Nature Cell Biology 11, 873 - 880 (2009)
Published online: 7 June 2009 | Corrected online: 2 July 2009 | doi:10.1038/ncb1896



There is a Erratum (August 2009) associated with this Letter.

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

Mirko H.H. Schmidt1,2, Frank Bicker2, Iva Nikolic2, Jeannette Meister2, Tanja Babuke1, Srdjan Picuric1, Werner Müller-Esterl1, Karl H. Plate2 & Ivan Dikic1

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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.

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  1. Institute of Biochemistry II, Johann Wolfgang Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
  2. Institute of Neurology, Johann Wolfgang Goethe University School of Medicine, Heinrich-Hoffmann-Str. 7, D-60528 Frankfurt am Main, Germany.

Correspondence to: Mirko H.H. Schmidt1,2 e-mail: Mirko.Schmidt@kgu.de

Correspondence to: Ivan Dikic1 e-mail: Ivan.Dikic@biochem2.de

* In the version of this article initially published online, the labelling of the yeast boxes in Fig. 1b was incorrect. In Fig. 1d the mNotch 2 values were missing, in Fig. 1g the Anti-EGFL7 was incorrectly labelled. In Fig 2c there was an extra '+' sign. In Fig 3d the title was incorrect. In Fig 5b the BSA label was missing from under the fifth bar. These errors have been corrected in the HTML and PDF versions of the article.

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