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Wnt7b signalling through Frizzled-7 receptor promotes dendrite development by coactivating CaMKII and JNK

Ferrari, ME; Bernis, ME; McLeod, F; Podpolny, M; Coullery, RP; Casadei, IM; Salinas, PC; (2018) Wnt7b signalling through Frizzled-7 receptor promotes dendrite development by coactivating CaMKII and JNK. Journal of Cell Science , 131 (13) , Article jcs216101. 10.1242/jcs.216101. Green open access

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Abstract

The formation of complex dendritic arbors is crucial for the assembly of functional networks as abnormal dendrite formation underlies several neurodevelopmental and psychiatric disorders. Many extracellular factors have been postulated as regulators of dendritic growth. Wnt proteins play a critical role in neuronal development and circuit formation. We previously demonstrated that Wnt7b acts through the scaffold protein dishevelled 1 (Dvl1) to modulate dendrite arborisation by activating a non-canonical Wnt signalling pathway. Here, we identify the seven-transmembrane frizzled-7 (Fz7, also known as FZD7) as the receptor for Wnt7b-mediated dendrite growth and complexity. Importantly, Fz7 is developmentally regulated in the intact hippocampus, and is localised along neurites and at dendritic growth cones, suggesting a role in dendrite formation and maturation. Fz7 loss-of-function studies demonstrated that Wnt7b requires Fz7 to promote dendritic arborisation. Moreover, in vivo Fz7 loss of function results in dendritic defects in the intact mouse hippocampus. Furthermore, our findings reveal that Wnt7b and Fz7 induce the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and JNK proteins, which are required for dendritic development. Here, we demonstrate that Wnt7b–Fz7 signals through two non-canonical Wnt pathways to modulate dendritic growth and complexity.

Type: Article
Title: Wnt7b signalling through Frizzled-7 receptor promotes dendrite development by coactivating CaMKII and JNK
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/jcs.216101
Publisher version: http://dx.doi.org/10.1242/jcs.216101
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Wnt signalling, Fz receptor, Dendrite development, Neuron, CaMKII, JNK
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10053868
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