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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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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 |
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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 |
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