Concentration-Dependent Requirement for Local Protein Synthesis in Motor Neuron Subtype-Specific Response to Axon Guidance Cues
| العنوان: | Concentration-Dependent Requirement for Local Protein Synthesis in Motor Neuron Subtype-Specific Response to Axon Guidance Cues |
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| المؤلفون: | Lance C. Kam, Hynek Wichterle, Mackenzie W. Amoroso, Mirza Peljto, Peng Shi, Stéphane Nedelec |
| المصدر: | The Journal of Neuroscience. 32:1496-1506 |
| بيانات النشر: | Society for Neuroscience, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Growth Cones, Nerve Tissue Proteins, Biology, Article, Mice, Semaphorin, medicine, Animals, Humans, Growth cone, Cells, Cultured, Embryonic Stem Cells, Motor Neurons, General Neuroscience, Compartment (ship), Membrane Proteins, Semaphorin-3A, SEMA3A, Motor neuron, Ephrin-A5, Axons, medicine.anatomical_structure, Spinal Cord, nervous system, Protein Biosynthesis, Axon guidance, Ephrin A5, Cues, Signal transduction, Neuroscience, Signal Transduction |
| الوصف: | Formation of functional motor circuits relies on the ability of distinct spinal motor neuron subtypes to project their axons with high precision to appropriate muscle targets. While guidance cues contributing to motor axon pathfinding have been identified, the intracellular pathways underlying subtype-specific responses to these cues remain poorly understood. In particular, it remains controversial whether responses to axon guidance cues depend on axonal protein synthesis. Using a growth cone collapse assay, we demonstrate that mouse embryonic stem cell-derived spinal motor neurons (ES-MNs) respond to ephrin-A5, Sema3f, and Sema3a in a concentration-dependent manner. At low doses, ES-MNs exhibit segmental or subtype-specific responses, while this selectivity is lost at higher concentrations. Response to high doses of semaphorins and to all doses of ephrin-A5 is protein synthesis independent. In contrast, using microfluidic devices and stripe assays, we show that growth cone collapse and guidance at low concentrations of semaphorins rely on local protein synthesis in the axonal compartment. Similar bimodal response to low and high concentrations of guidance cues is observed in human ES-MNs, pointing to a general mechanism by which neurons increase their repertoire of responses to the limited set of guidance cues involved in neural circuit formation. |
| تدمد: | 1529-2401 0270-6474 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22bf2427df32ad87f14946bfab67a761Test https://doi.org/10.1523/jneurosci.4176-11.2012Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....22bf2427df32ad87f14946bfab67a761 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292401 02706474 |
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