Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding
العنوان: | Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding |
---|---|
المؤلفون: | Peng Shi, Hynek Wichterle, Stéphane Nedelec, Lance C. Kam |
المصدر: | Lab on a Chip. 10:1005 |
بيانات النشر: | Royal Society of Chemistry (RSC), 2010. |
سنة النشر: | 2010 |
مصطلحات موضوعية: | Cell signaling, Growth Cones, Biomedical Engineering, Mice, Transgenic, Bioengineering, Nanotechnology, Biology, Biochemistry, Article, Mice, medicine, Biological neural network, Animals, Compartment (development), Axon, Growth cone, Cells, Cultured, Motor Neurons, Equipment Design, General Chemistry, Microfluidic Analytical Techniques, Cadherins, Receptors, Fibroblast Growth Factor, Embryonic stem cell, Equipment Failure Analysis, medicine.anatomical_structure, nervous system, Flow Injection Analysis, Biological Assay, Axon guidance, Neuron, Neuroscience, Protein Binding |
الوصف: | 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. |
تدمد: | 1473-0189 1473-0197 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::66de447d43a1c034a87cb3af434a2d1fTest https://doi.org/10.1039/b922143cTest |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....66de447d43a1c034a87cb3af434a2d1f |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14730189 14730197 |
---|