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Título:
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FLRT3 Is a Robo1-Interacting Protein that Determines Netrin-1 Attraction in Developing Axons
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Autor/a:
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Leyva-Díaz, Eduardo; Toro, Daniel del; Menal Castellote, Maria José; Cambray Carner, Serafí; Susín, Rafael; Tessier-Lavigne, Marc; Klein, Rüdiger; Egea Navarro, Joaquim; López-Bendito, Guillermina
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Notas:
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Background: Guidance molecules are normally presented to
cells in an overlapping fashion; however, little is known about
how their signals are integrated to control the formation of
neural circuits. In the thalamocortical system, the topographical
sorting of distinct axonal subpopulations relies on the
emergent cooperation between Slit1 and Netrin-1 guidance
cues presented by intermediate cellular targets. However,
the mechanism by which both cues interact to drive distinct
axonal responses remains unknown.
Results: Here, we show that the attractive response to the
guidance cue Netrin-1 is controlled by Slit/Robo1 signaling
and by FLRT3, a novel coreceptor for Robo1. While thalamic
axons lacking FLRT3 are insensitive to Netrin-1, thalamic
axons containing FLRT3 can modulate their Netrin-1 responsiveness
in a context-dependent manner. In the presence
of Slit1, both Robo1 and FLRT3 receptors are required to
induce Netrin-1 attraction by the upregulation of surface
DCC through the activation of protein kinase A. Finally, the
absence of FLRT3 produces defects in axon guidance in vivo.
Conclusions: These results highlight a novel mechanism by
which interactions between limited numbers of axon guidance
cues can multiply the responses in developing axons, as
required for proper axonal tract formation in the mammalian
brain.
This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB870 to R.K.), the Spanish MICINN (BFU2010-18055 to J.E. and BFU2012-34298 to G.L.-B.), FP7-PEOPLE-2011-CIG (PCIG9-GA-2011- 293980 to J.E.), the CONSOLIDER programme CSD2007-00023, and an ERC grant (ERC-2009-StG_20081210 to G.L.-B.). J.E. is a Ramón y Cajal investigator (RYC-2008-03342). G.L.-B. is an EMBO Young Investigator. |
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Derechos:
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(c) Elsevier Ltd., 2014
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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Elsevier
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Compartir:
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