Abstract
Synaptogenesis involves the transformation of dendritic filopodial contacts into stable connections with the exact apposition of synaptic components. Signalling triggered by Wnt/β-catenin and calcium has been postulated to aid this process. However, it is unclear how such a signalling process orchestrates synapse formation to organise the spatial arrangement of synapses along dendrites. We show that Wnt7a is loaded on dynamic dendritic filopodia during spine formation in human cortical neurons. Wnt7a is present at the tips of the filopodia and the contact sites with dendrites of neighbouring neurons, triggering spatially restricted localisation of the Wnt co-receptor Lrp6. Here, we find the induction of calcium transients, the clustering of pre- and postsynaptic proteins, and the subsequent transformation into mature spines. Although soluble Wnt7a protein can also support synaptogenesis, it fails to provide this degree of spatial information for spine formation and calcium transients and synaptic markers are induced ectopically along the dendrites. Our data suggest that dendritic filopodia are Wnt7a-bearing cytonemes required for focal calcium signalling, initiate synapse formation, and provide an elegant mechanism for orchestrating the positioning of synapses along dendrites.
Published Version
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