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

Dupin I, Lokmane L, Dahan M, Garel S, Studer V - Neural Dev (2015)

Bottom Line: In particular, it was recently found that the repellent Slit1 enables the attractive response of rostral thalamic axons to Netrin-1.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.

View Article: PubMed Central - PubMed

Affiliation: University Bordeaux, IINS, UMR 5297, F-33000, Bordeaux, France. isabelle.dupin@u-bordeaux.fr.

ABSTRACT

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.

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Subthreshold levels of the repellent Slit1 elicited Netrin-1 attraction or repulsion in specific axonal populations.
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Fig6: Subthreshold levels of the repellent Slit1 elicited Netrin-1 attraction or repulsion in specific axonal populations.

Mentions: Using these shear-free microfluidic devices, we investigated in detail the unexpected combinatorial activities of Slit1 and Netrin-1 on rostral thalamic axons [7]. We found that a steep Slit1 gradient (200 ng/ml in the reservoir, concentration range: 20 to 180 ng/ml) but not a shallower Slit1 gradient (50 ng/ml in the reservoir, concentration range: 5 to 45 ng/ml) promoted repulsion (Figure 6). In combinatorial conditions, we observed that Slit1 only elicited Netrin-1 attraction at subthreshold repulsion levels (Figure 6). Thus, in the absence of other guidance cues that may have a stronger effect on thalamic axons, Slit1 dictates the neuronal response to a Netrin-1 gradient. This observation is particularly relevant to assess axon pathfinding during brain development since growth cones can become responsive to Netrin-1 gradient only upon reaching a region of moderate Slit1 concentration.Figure 6


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

Dupin I, Lokmane L, Dahan M, Garel S, Studer V - Neural Dev (2015)

Subthreshold levels of the repellent Slit1 elicited Netrin-1 attraction or repulsion in specific axonal populations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4373007&req=5

Fig6: Subthreshold levels of the repellent Slit1 elicited Netrin-1 attraction or repulsion in specific axonal populations.
Mentions: Using these shear-free microfluidic devices, we investigated in detail the unexpected combinatorial activities of Slit1 and Netrin-1 on rostral thalamic axons [7]. We found that a steep Slit1 gradient (200 ng/ml in the reservoir, concentration range: 20 to 180 ng/ml) but not a shallower Slit1 gradient (50 ng/ml in the reservoir, concentration range: 5 to 45 ng/ml) promoted repulsion (Figure 6). In combinatorial conditions, we observed that Slit1 only elicited Netrin-1 attraction at subthreshold repulsion levels (Figure 6). Thus, in the absence of other guidance cues that may have a stronger effect on thalamic axons, Slit1 dictates the neuronal response to a Netrin-1 gradient. This observation is particularly relevant to assess axon pathfinding during brain development since growth cones can become responsive to Netrin-1 gradient only upon reaching a region of moderate Slit1 concentration.Figure 6

Bottom Line: In particular, it was recently found that the repellent Slit1 enables the attractive response of rostral thalamic axons to Netrin-1.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.

View Article: PubMed Central - PubMed

Affiliation: University Bordeaux, IINS, UMR 5297, F-33000, Bordeaux, France. isabelle.dupin@u-bordeaux.fr.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus