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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Nature Portfolio
2017
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oai:doaj.org-article:a1859b9f6ea446528bbd49524c971c622021-12-02T11:41:20ZThe Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis10.1038/s41598-017-06140-z2045-2322https://doaj.org/article/a1859b9f6ea446528bbd49524c971c622017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06140-zhttps://doaj.org/toc/2045-2322Abstract 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.Vanessa LanoueMichael LangfordAmanda WhiteKai SempertLily FoggHelen M. CooperNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q 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 |
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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. |
format |
article |
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 |
title |
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_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_sort |
wnt receptor ryk is a negative regulator of mammalian dendrite morphogenesis |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/a1859b9f6ea446528bbd49524c971c62 |
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