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

J Cell Sci. 2018 Jul 9;131(13):jcs216101. doi: 10.1242/jcs.216101.

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.

Keywords: CaMKII; Dendrite development; Fz receptor; JNK; Neuron; Wnt signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Dendrites / enzymology
  • Dendrites / genetics
  • Dendrites / metabolism*
  • Dishevelled Proteins / genetics
  • Dishevelled Proteins / metabolism
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neurites / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway

Substances

  • Dishevelled Proteins
  • Dvl1 protein, mouse
  • Fzd7 protein, mouse
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Wnt Proteins
  • Wnt7b protein, mouse
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • MAP Kinase Kinase 4