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

Vanessa Lanoue, Michael Langford, Amanda White, Kai Sempert, Lily Georgina Fogg, Helen Cooper (Corresponding Author)

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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.
Original languageEnglish
Article number5965
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 20 Jul 2017

Fingerprint

Wnt Receptors
Dendrites
Morphogenesis
Neuronal Plasticity
Growth
Somatosensory Cortex
Pyramidal Cells
Neurodegenerative Diseases
Neurons
Membranes
Brain

Keywords

  • cellular neuroscience
  • neuronal development

Cite this

Lanoue, V., Langford, M., White, A., Sempert, K., Fogg, L. G., & Cooper, H. (2017). The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis. Scientific Reports, 7, [5965]. https://doi.org/10.1038/s41598-017-06140-z

The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis. / Lanoue, Vanessa; Langford, Michael ; White, Amanda; Sempert, Kai; Fogg, Lily Georgina; Cooper, Helen (Corresponding Author).

In: Scientific Reports, Vol. 7, 5965, 20.07.2017.

Research output: Contribution to journalArticle

Lanoue, Vanessa ; Langford, Michael ; White, Amanda ; Sempert, Kai ; Fogg, Lily Georgina ; Cooper, Helen. / The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis. In: Scientific Reports. 2017 ; Vol. 7.
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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.",
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note = "This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (Grants 1061512, 1063080). ML and KS were supported by an Australian Postgraduate Award or a University of Queensland International Scholarship, respectively. Imaging work was performed in the Queensland Brain Institute’s Advanced Microscopy Facility and generously supported by an ARC LIEF grant (LE130100078). We thank Assoc. Prof. Julian Heng (Harry Perkins Institute of Medical Research, Perth, Australia) for providing the pCA-{\ss}-EGFPm5-Silencer 3 vector, Prof. Joseph LoTurco (University of Connecticut, USA) for the piggyBAC vector, and Prof. Steven Stacker (Peter MacCallum Cancer Centre, Melbourne, Australia) for providing the Ryk knockout mice and the full-length Ryk plasmid. We are also grateful to Mr Luke Hammond for expert advice on microscopy and Ms Rowan Tweedale for critical reading of the manuscript.",
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