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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Autores principales: Anna Kalinovsky, Fatiha Boukhtouche, Richard Blazeski, Caroline Bornmann, Noboru Suzuki, Carol A Mason, Peter Scheiffele
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/648ed5e2a7a04f50b1f85df18d8d63d2
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle 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
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