Cargando…

Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons

BACKGROUND: Axon pathfinding is controlled by guidance cues that elicit specific attractive or repulsive responses in growth cones. It has now become clear that some cues such as Netrin-1 can trigger either attraction or repulsion in a context-dependent manner. In particular, it was recently found t...

Descripción completa

Detalles Bibliográficos
Autores principales: Dupin, Isabelle, Lokmane, Ludmilla, Dahan, Maxime, Garel, Sonia, Studer, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373007/
https://www.ncbi.nlm.nih.gov/pubmed/25888985
http://dx.doi.org/10.1186/s13064-015-0036-8
_version_ 1782363273687990272
author Dupin, Isabelle
Lokmane, Ludmilla
Dahan, Maxime
Garel, Sonia
Studer, Vincent
author_facet Dupin, Isabelle
Lokmane, Ludmilla
Dahan, Maxime
Garel, Sonia
Studer, Vincent
author_sort Dupin, Isabelle
collection PubMed
description BACKGROUND: Axon pathfinding is controlled by guidance cues that elicit specific attractive or repulsive responses in growth cones. It has now become clear that some cues such as Netrin-1 can trigger either attraction or repulsion in a context-dependent manner. In particular, it was recently found that the repellent Slit1 enables the attractive response of rostral thalamic axons to Netrin-1. This finding raised the intriguing possibility that Netrin-1 and Slit1, two essential guidance cues, may act more generally in an unexpected combinatorial manner to orient specific axonal populations. To address this major issue, we have used an innovative microfluidic device compatible not only with dissociated neuronal cultures but also with explant cultures to systematically and quantitatively characterize the combinatorial activity of Slit1 and Netrin-1 on rostral thalamic axons as well as on hippocampal neurons. RESULTS: We found that on rostral thalamic axons, only a subthreshold concentration of the repellent Slit1 triggered an attractive response to a gradient of Netrin-1. On hippocampal neurons, we similarly found that Slit1 alone is repulsive and a subthreshold concentration of Slit1 triggered a potent attractive or repulsive behavioral response to a gradient of Netrin-1, depending on the nature of the substrate. CONCLUSIONS: Our study reveals that at subthreshold repulsive levels, Slit1 acts as a potent promoter of both Netrin-1 attractive and repulsive activities on distinct neuronal cell types, thereby opening novel perspectives on the role of combinations of cues in brain wiring. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13064-015-0036-8) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4373007
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-43730072015-03-26 Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons Dupin, Isabelle Lokmane, Ludmilla Dahan, Maxime Garel, Sonia Studer, Vincent Neural Dev Research Article BACKGROUND: Axon pathfinding is controlled by guidance cues that elicit specific attractive or repulsive responses in growth cones. It has now become clear that some cues such as Netrin-1 can trigger either attraction or repulsion in a context-dependent manner. In particular, it was recently found that the repellent Slit1 enables the attractive response of rostral thalamic axons to Netrin-1. This finding raised the intriguing possibility that Netrin-1 and Slit1, two essential guidance cues, may act more generally in an unexpected combinatorial manner to orient specific axonal populations. To address this major issue, we have used an innovative microfluidic device compatible not only with dissociated neuronal cultures but also with explant cultures to systematically and quantitatively characterize the combinatorial activity of Slit1 and Netrin-1 on rostral thalamic axons as well as on hippocampal neurons. RESULTS: We found that on rostral thalamic axons, only a subthreshold concentration of the repellent Slit1 triggered an attractive response to a gradient of Netrin-1. On hippocampal neurons, we similarly found that Slit1 alone is repulsive and a subthreshold concentration of Slit1 triggered a potent attractive or repulsive behavioral response to a gradient of Netrin-1, depending on the nature of the substrate. CONCLUSIONS: Our study reveals that at subthreshold repulsive levels, Slit1 acts as a potent promoter of both Netrin-1 attractive and repulsive activities on distinct neuronal cell types, thereby opening novel perspectives on the role of combinations of cues in brain wiring. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13064-015-0036-8) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-20 /pmc/articles/PMC4373007/ /pubmed/25888985 http://dx.doi.org/10.1186/s13064-015-0036-8 Text en © Dupin et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Dupin, Isabelle
Lokmane, Ludmilla
Dahan, Maxime
Garel, Sonia
Studer, Vincent
Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons
title Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons
title_full Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons
title_fullStr Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons
title_full_unstemmed Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons
title_short Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons
title_sort subrepellent doses of slit1 promote netrin-1 chemotactic responses in subsets of axons
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373007/
https://www.ncbi.nlm.nih.gov/pubmed/25888985
http://dx.doi.org/10.1186/s13064-015-0036-8
work_keys_str_mv AT dupinisabelle subrepellentdosesofslit1promotenetrin1chemotacticresponsesinsubsetsofaxons
AT lokmaneludmilla subrepellentdosesofslit1promotenetrin1chemotacticresponsesinsubsetsofaxons
AT dahanmaxime subrepellentdosesofslit1promotenetrin1chemotacticresponsesinsubsetsofaxons
AT garelsonia subrepellentdosesofslit1promotenetrin1chemotacticresponsesinsubsetsofaxons
AT studervincent subrepellentdosesofslit1promotenetrin1chemotacticresponsesinsubsetsofaxons