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

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, 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.

Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling

“…The effect of Wnt5a on morphogenesis of AHP‐derived neurons was also prevented by inhibition of CaMKII, suggesting that Wnt5a also signals through this Ca 2+ sensitive protein to modulate morphogenesis. Previous studies have involved CaMKII in activity‐dependent dendrite development of cultured hippocampal neurons, and in Wnt7b‐induced dendritogenesis in cultured pyramidal neurons . In addition, CaMKII is involved in Wnt5a‐dependent maintenance of dendritic arborization in CA1 pyramidal neurons of the adult hippocampus .…”

“…Previous studies have involved CaMKII in activity-dependent dendrite development of cultured hippocampal neurons, 76,77 and in Wnt7b-induced dendritogenesis in cultured pyramidal neurons. 78 In addition, CaMKII is involved in Wnt5a-dependent maintenance of dendritic arborization in CA1 pyramidal neurons of the adult hippocampus. 39 Therefore, it is likely that in the adult dentate gyrus, Wnt5a signals through the Wnt/CAMKII pathway to regulate morphogenesis of adult-born neuron.…”

Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells

“…Wnt7A-induced increase in luminal colony number requires FZD7 receptor FZD7 is a Wnt receptor shown to transduce both canonical and non-canonical Wnt signaling [265,[272][273][274][275][276][277][278]. To investigate the effect of Wnt signaling on luminal cell fate, the bipotent and luminal-restricted progenitor-enriched population were treated with a known canonical ligand Wnt3A or a non-canonical Wnt ligand Wnt7A [20,276].…”

“…FZD7 has been shown to play an important role in transducing both canonical and non-canonical Wnt signaling [265,[272][273][274][275][276][277][278] depending on the availability of the canonical and non-canonical Wnt ligands. For example, binding of Wnt7A to FZD7 receptor was shown to activate noncanonical Wnt signaling [276,279].…”

The Wnt/Ca 2+ pathway is involved in interneuronal communication mediated by tunneling nanotubes

“…In addition, βCaMKII inhibits actin polymerization by binding actin monomers and reducing the amount of freely available monomers (G‐actin) for nucleate polymer assembly (Sanabria et al , ). By controlling actin dynamics, Wnt pathway can regulate the formation of cellular protrusions, such as filopodia and lamellipodia, thus influencing dendritic spine outgrowth, as well as axonal spreading and enlargement of the axonal growth cone in developing neurons (Ciani et al , ; Stamatakou et al , ; Ferrari et al , ).…”