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

Yamagishi, S., Hampel, F., Hata, K., Del Toro Ruiz, D., Schwark, M., Kvachnina, E., et al. (2011). FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons. EMBO JOURNAL, 30(14), 2920-2933. doi:10.1038/emboj.2011.189.

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 Creators:
Yamagishi, Satoru1, Author              
Hampel, Falko1, Author              
Hata, Katsuhiko2, Author
Del Toro Ruiz, Daniel1, Author              
Schwark, Manuela2, Author
Kvachnina, Elena2, Author
Bastmeyer, Martin2, Author
Yamashita, Toshihide2, Author
Tarabykin, Victor2, Author
Klein, Rüdiger1, Author              
Egea, Joaquim1, Author              
Affiliations:
1Department: Molecular Neurobiology / Klein, MPI of Neurobiology, Max Planck Society, ou_1113546              
2External Organizations, ou_persistent22              

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Free keywords: C-6147-2008CELL-ADHESION; SUBVENTRICULAR ZONE; NEURITE OUTGROWTH; RECEPTOR GENE; AXON GUIDANCE; MIGRATION; MOLECULE; PROTEIN; IDENTIFICATION; SPECIFICATIONcell migration; cortex development; FLRT; repulsive guidance; Unc5;
 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 sub-ventricular 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. The EMBO Journal ( 2011) 30, 2920-2933. doi:10.1038/emboj.2011.189; Published online 14 June 2011

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Language(s): eng - English
 Dates: 2011
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000293970100017
DOI: 10.1038/emboj.2011.189
 Degree: -

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Title: EMBO JOURNAL
Source Genre: Journal
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Publ. Info: 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 30 (14) Sequence Number: - Start / End Page: 2920 - 2933 Identifier: ISSN: 0261-4189