FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons

Yamagishi, Satoru; Hampel, Falko; Hata, Katsuhiko; Toro, Daniel del; Schwark, Manuela; Kvachnina, Elena; Bastmeyer, Martin; Yamashita, Toshihide; Tarabykin, Victor; Klein, Rüdiger; Egea Navarro, Joaquim

doi:https://doi.org/10.1038/ emboj.2011.189

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Issue date

2011

Author

Yamagishi, Satoru

Hampel, Falko

Hata, Katsuhiko

Toro, Daniel del

Schwark, Manuela

Kvachnina, Elena

Bastmeyer, Martin

Yamashita, Toshihide

Tarabykin, Victor

Klein, Rüdiger

Egea Navarro, Joaquim

Suggested citation

Yamagishi, Satoru; Hampel, Falko; Hata, Katsuhiko; Toro, Daniel del; Schwark, Manuela; Kvachnina, Elena; ... Egea Navarro, Joaquim. (2011) . FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons. EMBO Journal, 2011, vol. 30, núm. 14. https://doi.org/10.1038/ emboj.2011.189.

Abstract

Netrin-1 induces repulsive axon guidance by binding to the mammalian Unc5 receptor family (Unc5A–Unc5D). Mouse genetic analysis of selected members of the Unc5 family, however, revealed essential functions independent of Netrin-1, suggesting the presence of other ligands. Unc5B was recently shown to bind fibronectin and leucine-rich transmembrane protein-3 (FLRT3), although the relevance of this interaction for nervous system development remained unclear. Here, we show that the related Unc5D receptor binds specifically to another FLRT protein, FLRT2. During development, FLRT2/3 ectodomains (ECDs) are shed from neurons and act as repulsive guidance molecules for axons and somata of Unc5-positive neurons. In the developing mammalian neocortex, Unc5D is expressed by neurons in the subventricular zone (SVZ), which display delayed migration to the FLRT2-expressing cortical plate (CP). Deletion of either FLRT2 or Unc5D causes a subset of SVZ-derived neurons to prematurely migrate towards the CP, whereas overexpression of Unc5D has opposite effects. Hence, the shed FLRT2 and FLRT3 ECDs represent a novel family of chemorepellents for Unc5-positive neurons and FLRT2/ Unc5D signalling modulates cortical neuron migration.

URI

http://hdl.handle.net/10459.1/57136

DOI

https://doi.org/10.1038/ emboj.2011.189

Is part of

EMBO Journal, 2011, vol. 30, núm. 14