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

Isabelle Dupin, Ludmilla Lokmane, Maxime Dahan, Sonia Garel, Vincent Studer
Neural Dev. 2015-03-20; 10(1):
DOI: 10.1186/s13064-015-0036-8

PubMed
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1. Neural Dev. 2015 Mar 20;10:5. doi: 10.1186/s13064-015-0036-8.

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

Dupin I(1)(2)(3), Lokmane L(4), Dahan M(5), Garel S(6), Studer V(7)(8).

Author information:
(1)University Bordeaux, IINS, UMR 5297, F-33000, Bordeaux, France.
.
(2)CNRS, IINS, UMR 5297, F-33000, Bordeaux, France. .
(3)Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC 0005, INSERM,
University Bordeaux, F-33000, Bordeaux, France. .
(4)ENS, IBENS, INSERM U1024, CNRS UMR8197, 46 rue d’Ulm, 75005, Paris, France.
.
(5)Institut Curie, Laboratoire de Physico-Chimie, CNRS UMR 168, Université Pierre
et Marie Curie-Paris 6, 75005, Paris, France. .
(6)ENS, IBENS, INSERM U1024, CNRS UMR8197, 46 rue d’Ulm, 75005, Paris, France.
.
(7)University Bordeaux, IINS, UMR 5297, F-33000, Bordeaux, France.
.
(8)CNRS, IINS, UMR 5297, F-33000, Bordeaux, France. .

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.

DOI: 10.1186/s13064-015-0036-8
PMCID: PMC4373007
PMID: 25888985 [Indexed for MEDLINE]

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