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Issue 8, 2010
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Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding

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Abstract

Assembly of functional neural circuits relies on the ability of axons to navigate a complex landscape of guidance cues in the extracellular environment. In this report, we investigate localized cell signaling in response to these cues by combining a microfabricated compartmentalization chamber with multicomponent, protein-micropatterned surfaces; this system offers improved spatial resolution and new capabilities for targeted manipulation of neuronal axons. We illustrate the potential of this system by addressing the role of fibroblast growth factor receptor (FGFR) signaling in modulating axon guidance by N-cadherin. Motor neurons that were derived from embryonic stem cells extend axons from one compartment through a microchannel barrier and into a second compartment containing patterns of N-cadherin, against a background of laminin. N-cadherin was effective in both guiding and accelerating motor axon outgrowth. Using the chamber system to target the application of pharmacological agents to specific parts of the neuron, we demonstrate that FGFR signaling in the axon but not the cell body increases the rate of axon outgrowth while not affecting guidance along N-cadherin. These results demonstrate that cell signaling must take into account the spatial layout of the cell. This new platform provides a powerful tool for understanding such effects over a wide range of signaling systems.

Graphical abstract: Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding

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Publication details

The article was received on 23 Oct 2009, accepted on 05 Jan 2010 and first published on 25 Jan 2010


Article type: Paper
DOI: 10.1039/B922143C
Citation: Lab Chip, 2010,10, 1005-1010
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    Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding

    P. Shi, S. Nedelec, H. Wichterle and L. C. Kam, Lab Chip, 2010, 10, 1005
    DOI: 10.1039/B922143C

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