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Título:
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FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons
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Autor/a:
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Yamagishi, Satoru; Hampel, Falko; Hata, Katsuhiko; Toro, Daniel del; Schwark, Manuela; Kvachnina, Elena; Bastmeyer, Martin; Yamashita, Toshihide; Tarabykin, Victor; Klein, Rüdiger; Egea Navarro, Joaquim
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Notas:
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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.
This work was in part funded by the Max Planck Society (to RK and VT), by the Deutsche Forschungsgemeinschaft (SFB665 and Heisenberg Program to VT) and by the Generalitat de Catalunya (SGR740) and Ministerio de Ciencia e Innovación (BFU2010-18055) (to JE). |
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Materia(s):
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-Cell migration
-Cortex development
-FLRT |
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Derechos:
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(c) EMBO Press, 2011
info:eu-repo/semantics/restrictedAccess |
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Tipo de documento:
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article
publishedVersion |
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Editor:
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EMBO Press
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Compartir:
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