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Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways

Wnt signaling represents a highly versatile signaling system, which plays diverse and critical roles in various aspects of neural development. Sensory neurons of the dorsal root ganglia require Wnt signaling for initial cell-fate determination as well as patterning and synapse formation. Here we rep...

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Bibliographic Details
Main Authors: Simonetti, Manuela (Author) , Agarwal, Nitin (Author) , Bali, Kiran Kumar (Author) , Niehrs, Christof (Author) , Kuner, Rohini (Author)
Format: Article (Journal)
Language:English
Published: 2 July 2014
In: Neuron
Year: 2014, Volume: 83, Issue: 1, Pages: 104-121
ISSN:1097-4199
DOI:10.1016/j.neuron.2014.05.037
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.neuron.2014.05.037
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0896627314004528
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Author Notes:Manuela Simonetti, Nitin Agarwal, Sebastian Stösser, Kiran Kumar Bali, Emil Karaulanov, Rashmi Kamble, Blanka Pospisilova, Martina Kurejova, Walter Birchmeier, Christof Niehrs, Paul Heppenstall, and Rohini Kuner
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Summary:Wnt signaling represents a highly versatile signaling system, which plays diverse and critical roles in various aspects of neural development. Sensory neurons of the dorsal root ganglia require Wnt signaling for initial cell-fate determination as well as patterning and synapse formation. Here we report that Wnt signaling pathways persist in adult sensory neurons and play a functional role in their sensitization in a pathophysiological context. We observed that Wnt3a recruits the Wnt-calcium signaling pathway and the Wnt planar cell polarity pathway in peripheral nerves to alter pain sensitivity in a modality-specific manner and we elucidated underlying mechanisms. In contrast, biochemical, pharmacological, and genetic studies revealed lack of functional relevance for the classical canonical β-catenin pathway in peripheral sensory neurons in acute modulation of nociception. Finally, this study provides proof-of-concept for a translational potential for Wnt3a-Frizzled3 signaling in alleviating disease-related pain hypersensitivity in cancer-associated pain in vivo.
Item Description:Gesehen am 07.08.2020
Physical Description:Online Resource
ISSN:1097-4199
DOI:10.1016/j.neuron.2014.05.037

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