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

Abstract 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, ho...

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Main Authors: Vanessa Lanoue, Michael Langford, Amanda White, Kai Sempert, Lily Fogg, Helen M. Cooper
Format: Article
Language:English
Published: Nature Portfolio 2017-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-06140-z
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author Vanessa Lanoue
Michael Langford
Amanda White
Kai Sempert
Lily Fogg
Helen M. Cooper
author_facet Vanessa Lanoue
Michael Langford
Amanda White
Kai Sempert
Lily Fogg
Helen M. Cooper
author_sort Vanessa Lanoue
collection DOAJ
description Abstract 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 doaj.art-a1859b9f6ea446528bbd49524c971c622022-12-21T20:28:44ZengNature PortfolioScientific Reports2045-23222017-07-017111110.1038/s41598-017-06140-zThe Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesisVanessa Lanoue0Michael Langford1Amanda White2Kai Sempert3Lily Fogg4Helen M. Cooper5The University of Queensland, Queensland Brain InstituteThe University of Queensland, Queensland Brain InstituteThe University of Queensland, Queensland Brain InstituteThe University of Queensland, Queensland Brain InstituteThe University of Queensland, Queensland Brain InstituteThe University of Queensland, Queensland Brain InstituteAbstract 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.https://doi.org/10.1038/s41598-017-06140-z
spellingShingle Vanessa Lanoue
Michael Langford
Amanda White
Kai Sempert
Lily Fogg
Helen M. Cooper
The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis
Scientific Reports
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
url https://doi.org/10.1038/s41598-017-06140-z
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