Development of axon-target specificity of ponto-cerebellar afferents.
The function of neuronal networks relies on selective assembly of synaptic connections during development. We examined how synaptic specificity emerges in the pontocerebellar projection. Analysis of axon-target interactions with correlated light-electron microscopy revealed that developing pontine m...
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2011
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oai:doaj.org-article:648ed5e2a7a04f50b1f85df18d8d63d22021-11-18T05:36:20ZDevelopment of axon-target specificity of ponto-cerebellar afferents.1544-91731545-788510.1371/journal.pbio.1001013https://doaj.org/article/648ed5e2a7a04f50b1f85df18d8d63d22011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21346800/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The function of neuronal networks relies on selective assembly of synaptic connections during development. We examined how synaptic specificity emerges in the pontocerebellar projection. Analysis of axon-target interactions with correlated light-electron microscopy revealed that developing pontine mossy fibers elaborate extensive cell-cell contacts and synaptic connections with Purkinje cells, an inappropriate target. Subsequently, mossy fiber-Purkinje cell connections are eliminated resulting in granule cell-specific mossy fiber connectivity as observed in mature cerebellar circuits. Formation of mossy fiber-Purkinje cell contacts is negatively regulated by Purkinje cell-derived BMP4. BMP4 limits mossy fiber growth in vitro and Purkinje cell-specific ablation of BMP4 in mice results in exuberant mossy fiber-Purkinje cell interactions. These findings demonstrate that synaptic specificity in the pontocerebellar projection is achieved through a stepwise mechanism that entails transient innervation of Purkinje cells, followed by synapse elimination. Moreover, this work establishes BMP4 as a retrograde signal that regulates the axon-target interactions during development.Anna KalinovskyFatiha BoukhtoucheRichard BlazeskiCaroline BornmannNoboru SuzukiCarol A MasonPeter ScheiffelePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 9, Iss 2, p e1001013 (2011) |
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DOAJ |
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Biology (General) QH301-705.5 |
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Biology (General) QH301-705.5 Anna Kalinovsky Fatiha Boukhtouche Richard Blazeski Caroline Bornmann Noboru Suzuki Carol A Mason Peter Scheiffele Development of axon-target specificity of ponto-cerebellar afferents. |
description |
The function of neuronal networks relies on selective assembly of synaptic connections during development. We examined how synaptic specificity emerges in the pontocerebellar projection. Analysis of axon-target interactions with correlated light-electron microscopy revealed that developing pontine mossy fibers elaborate extensive cell-cell contacts and synaptic connections with Purkinje cells, an inappropriate target. Subsequently, mossy fiber-Purkinje cell connections are eliminated resulting in granule cell-specific mossy fiber connectivity as observed in mature cerebellar circuits. Formation of mossy fiber-Purkinje cell contacts is negatively regulated by Purkinje cell-derived BMP4. BMP4 limits mossy fiber growth in vitro and Purkinje cell-specific ablation of BMP4 in mice results in exuberant mossy fiber-Purkinje cell interactions. These findings demonstrate that synaptic specificity in the pontocerebellar projection is achieved through a stepwise mechanism that entails transient innervation of Purkinje cells, followed by synapse elimination. Moreover, this work establishes BMP4 as a retrograde signal that regulates the axon-target interactions during development. |
format |
article |
author |
Anna Kalinovsky Fatiha Boukhtouche Richard Blazeski Caroline Bornmann Noboru Suzuki Carol A Mason Peter Scheiffele |
author_facet |
Anna Kalinovsky Fatiha Boukhtouche Richard Blazeski Caroline Bornmann Noboru Suzuki Carol A Mason Peter Scheiffele |
author_sort |
Anna Kalinovsky |
title |
Development of axon-target specificity of ponto-cerebellar afferents. |
title_short |
Development of axon-target specificity of ponto-cerebellar afferents. |
title_full |
Development of axon-target specificity of ponto-cerebellar afferents. |
title_fullStr |
Development of axon-target specificity of ponto-cerebellar afferents. |
title_full_unstemmed |
Development of axon-target specificity of ponto-cerebellar afferents. |
title_sort |
development of axon-target specificity of ponto-cerebellar afferents. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/648ed5e2a7a04f50b1f85df18d8d63d2 |
work_keys_str_mv |
AT annakalinovsky developmentofaxontargetspecificityofpontocerebellarafferents AT fatihaboukhtouche developmentofaxontargetspecificityofpontocerebellarafferents AT richardblazeski developmentofaxontargetspecificityofpontocerebellarafferents AT carolinebornmann developmentofaxontargetspecificityofpontocerebellarafferents AT noborusuzuki developmentofaxontargetspecificityofpontocerebellarafferents AT carolamason developmentofaxontargetspecificityofpontocerebellarafferents AT peterscheiffele developmentofaxontargetspecificityofpontocerebellarafferents |
_version_ |
1718424915546210304 |