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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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2 July 2014
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| 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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| 245 | 1 | 0 | |a Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways |c 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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| 520 | |a 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. | ||
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