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The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis

The unique dendritic architecture of a given neuronal subtype determines its synaptic connectivity and ability to integrate into functional neuronal networks. It is now clear that abnormal dendritic structure is associated with neuropsychiatric and neurodegenerative disorders. Currently, however, th...

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Autores principales: Lanoue, Vanessa, Langford, Michael, White, Amanda, Sempert, Kai, Fogg, Lily, Cooper, Helen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519545/
https://www.ncbi.nlm.nih.gov/pubmed/28729735
http://dx.doi.org/10.1038/s41598-017-06140-z
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author Lanoue, Vanessa
Langford, Michael
White, Amanda
Sempert, Kai
Fogg, Lily
Cooper, Helen M.
author_facet Lanoue, Vanessa
Langford, Michael
White, Amanda
Sempert, Kai
Fogg, Lily
Cooper, Helen M.
author_sort Lanoue, Vanessa
collection PubMed
description The unique dendritic architecture of a given neuronal subtype determines its synaptic connectivity and ability to integrate into functional neuronal networks. It is now clear that abnormal dendritic structure is associated with neuropsychiatric and neurodegenerative disorders. Currently, however, the nature of the extrinsic factors that limit dendritic growth and branching within predetermined boundaries in the mammalian brain is poorly understood. Here we identify the Wnt receptor Ryk as a novel negative regulator of dendritic arborisation. We demonstrate that loss of Ryk in mouse hippocampal and cortical neurons promotes excessive dendrite growth and branching in vitro. Conversely, overexpression of wildtype Ryk restricts these processes, confirming that Ryk acts to restrain dendrite arborisation. Furthermore, we identify a hitherto uncharacterized membrane proximal subdomain crucial for Ryk-mediated suppression of dendrite morphogenesis, suggesting that it may act through a novel signalling pathway to constrain dendrite complexity. We also demonstrate that Ryk performs a similar function in vivo as Ryk haploinsufficient postnatal animals exhibit excessive dendrite growth and branching in layer 2/3 pyramidal neurons of the somatosensory cortex. These findings reveal an essential role for Ryk in regulating dendrite complexity and raise the intriguing possibility that it may influence neural plasticity by modifying dendritic structure.
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spelling pubmed-55195452017-07-21 The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis Lanoue, Vanessa Langford, Michael White, Amanda Sempert, Kai Fogg, Lily Cooper, Helen M. Sci Rep Article The unique dendritic architecture of a given neuronal subtype determines its synaptic connectivity and ability to integrate into functional neuronal networks. It is now clear that abnormal dendritic structure is associated with neuropsychiatric and neurodegenerative disorders. Currently, however, the nature of the extrinsic factors that limit dendritic growth and branching within predetermined boundaries in the mammalian brain is poorly understood. Here we identify the Wnt receptor Ryk as a novel negative regulator of dendritic arborisation. We demonstrate that loss of Ryk in mouse hippocampal and cortical neurons promotes excessive dendrite growth and branching in vitro. Conversely, overexpression of wildtype Ryk restricts these processes, confirming that Ryk acts to restrain dendrite arborisation. Furthermore, we identify a hitherto uncharacterized membrane proximal subdomain crucial for Ryk-mediated suppression of dendrite morphogenesis, suggesting that it may act through a novel signalling pathway to constrain dendrite complexity. We also demonstrate that Ryk performs a similar function in vivo as Ryk haploinsufficient postnatal animals exhibit excessive dendrite growth and branching in layer 2/3 pyramidal neurons of the somatosensory cortex. These findings reveal an essential role for Ryk in regulating dendrite complexity and raise the intriguing possibility that it may influence neural plasticity by modifying dendritic structure. Nature Publishing Group UK 2017-07-20 /pmc/articles/PMC5519545/ /pubmed/28729735 http://dx.doi.org/10.1038/s41598-017-06140-z Text en © The Author(s) 2017 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/.
spellingShingle Article
Lanoue, Vanessa
Langford, Michael
White, Amanda
Sempert, Kai
Fogg, Lily
Cooper, Helen M.
The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis
title The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis
title_full The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis
title_fullStr The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis
title_full_unstemmed The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis
title_short The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis
title_sort wnt receptor ryk is a negative regulator of mammalian dendrite morphogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519545/
https://www.ncbi.nlm.nih.gov/pubmed/28729735
http://dx.doi.org/10.1038/s41598-017-06140-z
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