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      Sema7A/PlxnCl signaling triggers activity-dependent olfactory synapse formation

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          Abstract

          In mammals, neural circuits are formed based on a genetic program and further refined by neuronal activity during the neonatal period. We report that in the mouse olfactory system, the glomerular map is not merely refined but newly connected to second-order neurons by odorant-receptor-derived neuronal activity. Here, we analyzed a pair of molecules, Sema7A, expressed in olfactory sensory neurons (OSNs) in an activity-dependent manner, and PlxnC1, localized to dendrites of mitral/tufted (M/T) cells in the first week after birth. In Sema7A or PlxnC1 knockout (KO) mice, initiation of synapse formation and dendrite selection of M/T cells were perturbed. Reconstitution and rescue experiments demonstrated that Sema7A–PlxnC1 interaction is essential to form the post-synaptic assembly. Pharmacological blocking experiments indicated that synaptic transmission triggers primary dendrite selection by synaptic competition. We conclude that Sema7A signaling is key to inducing activity-dependent post-synapse events and dendrite selection in M/T-cells during the neonatal period.

          Abstract

          The molecular mechanisms underlying synapse formation in the olfactory bulb are not fully understood. Here the authors demonstrate that semaphorin 7A on olfactory sensory neurons, and its receptor plexin C1 expressed on mitral and tufted cells, is required for correct synapse formation.

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          Most cited references36

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          Combinatorial receptor codes for odors.

          The discriminatory capacity of the mammalian olfactory system is such that thousands of volatile chemicals are perceived as having distinct odors. Here we used a combination of calcium imaging and single-cell RT-PCR to identify odorant receptors (ORs) for odorants with related structures but varied odors. We found that one OR recognizes multiple odorants and that one odorant is recognized by multiple ORs, but that different odorants are recognized by different combinations of ORs. Thus, the olfactory system uses a combinatorial receptor coding scheme to encode odor identities. Our studies also indicate that slight alterations in an odorant, or a change in its concentration, can change its "code," potentially explaining how such changes can alter perceived odor quality.
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            Development of the vertebrate neuromuscular junction.

            We describe the formation, maturation, elimination, maintenance, and regeneration of vertebrate neuromuscular junctions (NMJs), the best studied of all synapses. The NMJ forms in a series of steps that involve the exchange of signals among its three cellular components--nerve terminal, muscle fiber, and Schwann cell. Although essentially any motor axon can form NMJs with any muscle fiber, an additional set of cues biases synapse formation in favor of appropriate partners. The NMJ is functional at birth but undergoes numerous alterations postnatally. One step in maturation is the elimination of excess inputs, a competitive process in which the muscle is an intermediary. Once elimination is complete, the NMJ is maintained stably in a dynamic equilibrium that can be perturbed to initiate remodeling. NMJs regenerate following damage to nerve or muscle, but this process differs in fundamental ways from embryonic synaptogenesis. Finally, we consider the extent to which the NMJ is a suitable model for development of neuron-neuron synapses.
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              Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates.

              In Drosophila, plexin A is a functional receptor for semaphorin-1a. Here we show that the human plexin gene family comprises at least nine members in four subfamilies. Plexin-B1 is a receptor for the transmembrane semaphorin Sema4D (CD100), and plexin-C1 is a receptor for the GPI-anchored semaphorin Sema7A (Sema-K1). Secreted (class 3) semaphorins do not bind directly to plexins, but rather plexins associate with neuropilins, coreceptors for these semaphorins. Plexins are widely expressed: in neurons, the expression of a truncated plexin-A1 protein blocks axon repulsion by Sema3A. The cytoplasmic domain of plexins associates with a tyrosine kinase activity. Plexins may also act as ligands mediating repulsion in epithelial cells in vitro. We conclude that plexins are receptors for multiple (and perhaps all) classes of semaphorins, either alone or in combination with neuropilins, and trigger a novel signal transduction pathway controlling cell repulsion.
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                Author and article information

                Contributors
                sakano.hts@gmail.com
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                9 May 2018
                9 May 2018
                2018
                : 9
                : 1842
                Affiliations
                [1 ]ISNI 0000 0001 0692 8246, GRID grid.163577.1, Department of Brain Function, , University of Fukui School of Medicine, ; 23-3 Shimo-aizuki, Matsuoka, Fukui, 910-1193 Japan
                [2 ]ISNI 0000 0001 2151 536X, GRID grid.26999.3d, Department of Physiology, Graduate School of Medicine, , The University of Tokyo, ; 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
                [3 ]ISNI 0000000094465255, GRID grid.7597.c, RIKEN Institute, ; 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047 Japan
                Article
                4239
                10.1038/s41467-018-04239-z
                5943276
                29743476
                59b1fecb-df52-414d-ab0d-ac07b028c93d
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 October 2017
                : 13 April 2018
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