Distinct sets of FGF receptors sculpt excitatory and inhibitory synaptogenesis
| العنوان: | Distinct sets of FGF receptors sculpt excitatory and inhibitory synaptogenesis |
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| المؤلفون: | Ania Dabrowski, Cameron Strong, Akiko Terauchi, Hisashi Umemori |
| المصدر: | Development. 142:1818-1830 |
| بيانات النشر: | The Company of Biologists, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | FGF22, Neurogenesis, Synaptogenesis, Biology, Inhibitory postsynaptic potential, Mice, Excitatory synapse, Animals, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Fibroblast Growth Factor, Type 2, Receptor, Molecular Biology, Cells, Cultured, Mice, Knockout, Neurons, Cell Differentiation, Receptors, Fibroblast Growth Factor, Cell biology, Fibroblast Growth Factors, nervous system, Fibroblast growth factor receptor, Synapses, Commentary, Excitatory postsynaptic potential, Signal transduction, Research Article, Developmental Biology |
| الوصف: | Neurons in the brain must establish a balanced network of excitatory and inhibitory synapses during development for the brain to function properly. An imbalance between these synapses underlies various neurological and psychiatric disorders. The formation of excitatory and inhibitory synapses requires precise molecular control. In the hippocampus, the structure crucial for learning and memory, fibroblast growth factor 22 (FGF22) and FGF7 specifically promote excitatory or inhibitory synapse formation, respectively. Knockout of either Fgf gene leads to excitatory-inhibitory imbalance in the mouse hippocampus and manifests in an altered susceptibility to epileptic seizures, underscoring the importance of FGF-dependent synapse formation. However, the receptors and signaling mechanisms by which FGF22 and FGF7 induce excitatory and inhibitory synapse differentiation are unknown. Here, we show that distinct sets of overlapping FGF receptors (FGFRs), FGFR2b and FGFR1b, mediate excitatory or inhibitory presynaptic differentiation in response to FGF22 and FGF7. Excitatory presynaptic differentiation is impaired in Fgfr2b and Fgfr1b mutant mice; however, inhibitory presynaptic defects are only found in Fgfr2b mutants. FGFR2b and FGFR1b are required for an excitatory presynaptic response to FGF22, whereas only FGFR2b is required for an inhibitory presynaptic response to FGF7. We further find that FGFRs are required in the presynaptic neuron to respond to FGF22, and that FRS2 and PI3K, but not PLCγ, mediate FGF22-dependent presynaptic differentiation. Our results reveal the specific receptors and signaling pathways that mediate FGF-dependent presynaptic differentiation, and thereby provide a mechanistic understanding of precise excitatory and inhibitory synapse formation in the mammalian brain. |
| تدمد: | 1477-9129 0950-1991 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47e2a5187a7c76b94e7cf2fb5c1f6ea3 https://doi.org/10.1242/dev.115568 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....47e2a5187a7c76b94e7cf2fb5c1f6ea3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779129 09501991 |
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