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

• Published in: Journal of cell science Vol. 131; no. 13; p. jcs216101
• Main Authors: Ferrari, María E, Bernis, María E, McLeod, Faye, Podpolny, Marina, Coullery, Romina P, Casadei, Inelia M, Salinas, Patricia C, Rosso, Silvana B
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01-07-2018
• Subjects: Animals; Axonogenesis; Ca2+/calmodulin-dependent protein kinase II; Calcium ions; Calcium-binding protein; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Calmodulin; Cascades; Complexity; Cones; Dendrites - enzymology; Dendrites - genetics; Dendrites - metabolism; Dendritic structure; Dishevelled protein; Dishevelled Proteins - genetics; Dishevelled Proteins - metabolism; Frizzled protein; Frizzled Receptors; Growth cones; Hippocampus; Hippocampus - growth & development; Hippocampus - metabolism; In vivo methods and tests; JNK protein; Kinases; MAP Kinase Kinase 4 - genetics; MAP Kinase Kinase 4 - metabolism; Mental disorders; Mice; Mice, Inbred C57BL; Neurites - metabolism; Neurodevelopmental disorders; Phosphorylation; Protein Binding; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Rats; Rats, Wistar; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Regulators; Signal transduction; Signaling; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Signaling Pathway; CaMKII; Neuron; Wnt signalling; Dendrite development; Fz receptor; JNK
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.216101

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,
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 Ca
/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.