Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons
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  • 作者:Isabelle Dupin (1) (2) (5)
    Ludmilla Lokmane (3)
    Maxime Dahan (4)
    Sonia Garel (3)
    Vincent Studer (1) (2)

    1. University Bordeaux
    ; IINS ; UMR 5297 ; F-33000 ; Bordeaux ; France
    2. CNRS
    ; IINS ; UMR 5297 ; F-33000 ; Bordeaux ; France
    5. Centre de Recherche Cardio-thoracique de Bordeaux
    ; U1045 ; CIC 0005 ; INSERM ; University Bordeaux ; F-33000 ; Bordeaux ; France
    3. ENS
    ; IBENS ; INSERM U1024 ; CNRS UMR8197 ; 46 rue d鈥橴lm ; 75005 ; Paris ; France
    4. Institut Curie
    ; Laboratoire de Physico-Chimie ; CNRS UMR 168 ; Universit茅 Pierre et Marie Curie-Paris 6 ; 75005 ; Paris ; France
  • 关键词:Axon guidance ; Microfluidic ; Netrin ; 1 ; Slit1 ; Thalamic neurons ; Hippocampal neurons
  • 刊名:Neural Development
  • 出版年:2015
  • 出版时间:December 2015
  • 年:2015
  • 卷:10
  • 期:1
  • 全文大小:2,813 KB
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    8. Dupin, I, Dahan, M, Studer, V (2013) Investigating axonal guidance with microdevice-based approaches. J Neurosci 33: pp. 17647-55 CrossRef
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    13. Rosoff, WJ, Urbach, JS, Esrick, MA, McAllister, RG, Richards, LJ, Goodhill, GJ (2004) A new chemotaxis assay shows the extreme sensitivity of axons to molecular gradients. Nat Neurosci 7: pp. 678-82 CrossRef
    14. Leyva-Diaz, E, Toro, D, Menal, MJ, Cambray, S, Susin, R, Tessier-Lavigne, M (2014) FLRT3 is a Robo1-interacting protein that determines Netrin-1 attraction in developing axons. Curr Biol 24: pp. 494-508 CrossRef
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    16. Bartoe, JL, McKenna, WL, Quan, TK, Stafford, BK, Moore, JA, Xia, J (2006) Protein interacting with C-kinase 1/protein kinase Calpha-mediated endocytosis converts netrin-1-mediated repulsion to attraction. J Neurosci 26: pp. 3192-205 CrossRef
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  • 刊物主题:Neurosciences; Developmental Biology;
  • 出版者:BioMed Central
  • ISSN:1749-8104
文摘
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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