Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons
| العنوان: | Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons |
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| المؤلفون: | Louis-Philippe Croteau, Dayana Krawchuk, Frédéric Charron, Daniel Morales, Jean-François Cloutier, Artur Kania, Sebastian Poliak, Susan L. Ackerman, Matthew B. Dalva, Elena Palmesino, Susan Morton, Tzu-Jen Kao |
| المصدر: | eLife eLife, Vol 4 (2015) |
| بيانات النشر: | eLife Sciences Publications, Ltd, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | animal structures, Mouse, QH301-705.5, Receptor, EphB2, Science, Growth Cones, synergy, Ephrin-B2, Receptors, Nerve Growth Factor, Biology, General Biochemistry, Genetics and Molecular Biology, Mice, Netrin, medicine, Animals, Ephrin, Nerve Growth Factors, Biology (General), Axon, Growth cone, Motor Neurons, General Immunology and Microbiology, axon guidance, Tumor Suppressor Proteins, General Neuroscience, fungi, Erythropoietin-producing hepatocellular (Eph) receptor, General Medicine, Anatomy, Netrin-1, Motor neuron, Spinal cord, Chicken, ephrin, Developmental Biology and Stem Cells, medicine.anatomical_structure, nervous system, embryonic structures, Medicine, Axon guidance, Netrin Receptors, Neuroscience, Signal Transduction, Research Article |
| الوصف: | During neural circuit assembly, axonal growth cones are exposed to multiple guidance signals at trajectory choice points. While axonal responses to individual guidance cues have been extensively studied, less is known about responses to combination of signals and underlying molecular mechanisms. Here, we studied the convergence of signals directing trajectory selection of spinal motor axons entering the limb. We first demonstrate that Netrin-1 attracts and repels distinct motor axon populations, according to their expression of Netrin receptors. Quantitative in vitro assays demonstrate that motor axons synergistically integrate both attractive or repulsive Netrin-1 signals together with repulsive ephrin signals. Our investigations of the mechanism of ephrin-B2 and Netrin-1 integration demonstrate that the Netrin receptor Unc5c and the ephrin receptor EphB2 can form a complex in a ligand-dependent manner and that Netrin–ephrin synergistic growth cones responses involve the potentiation of Src family kinase signaling, a common effector of both pathways. DOI: http://dx.doi.org/10.7554/eLife.10841.001Test eLife digest The ability of animals to walk and perform skilled movements depends on particular groups of muscles contracting in a coordinated manner. Muscles are activated by nerve cells called motor neurons found in the spinal cord. The connections between the motor neurons and muscles are established in the developing embryo. Each motor neuron produces a long projection called an axon whose growth is guided towards the target muscle by signal proteins. The motor neurons are exposed to many such signal proteins at the same time and it is not clear how they integrate all this information so that their axons target the correct muscles. Poliak, Morales et al. used a variety of genetic and biochemical approaches to study the formation of motor neuron and muscle connections in the limbs of mice and chicks. The experiments show that a signal protein called Netrin-1 is produced in the limbs of developing embryos and attracts the axons of some types of motor neurons and repels others. This is due to the motor neurons producing different types of receptor proteins to detect Netrin-1. Further experiments show that individual axons can combine information from attractive or repulsive Netrin-1 signals together with repulsive signals from another family of proteins called ephrins in a 'synergistic' manner. That is, the combined effect of both cues is stronger than their individual effects added together. This synergy involves ligand-dependent interactions between the Netrin-1 and ephrin receptor proteins, and the activation of a common enzyme. Poliak, Morales et al.’s findings reveal a new role for Netrin-1 in guiding the development of motor neurons in the limb. Future work will focus on further understanding the mechanism of synergy between Netrin-1 and ephrins. Netrin-1 and ephrins are also involved in the formation of blood vessels and many other developmental processes, so understanding how they work together would have a wide-reaching impact on research into human health and disease. DOI: http://dx.doi.org/10.7554/eLife.10841.002Test |
| تدمد: | 2050-084X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1678f51f6b0a9e60f967bff4d2874d77Test https://doi.org/10.7554/elife.10841Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1678f51f6b0a9e60f967bff4d2874d77 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
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