Wnt signalling in the development of axon, dendrites and synapses

Abstract

Wnts are a highly conserved family of secreted glycoproteins that play essential roles in the morphogenesis and body patterning during the development of metazoan species. In recent years, mounting evidence has revealed important functions of Wnt signalling in diverse aspects of neural development, including neuronal polarization, guidance and branching of the axon and dendrites, as well as synapse formation and its structural remodelling. In contrast to Wnt signalling in cell proliferation and differentiation, which mostly acts through β-catenin-dependent pathways, Wnts engage a diverse array of non-transcriptional cascades in neuronal development, such as the planar cell polarity, cytoskeletal or calcium signalling pathways. In this review, we summarize recent advances in the mechanisms of Wnt signalling in the development of axon, dendrite and synapse formation.

No Longer Underappreciated: The Emerging Concept of Astrocyte Heterogeneity in Neuroscience

“…Recent evidence now suggests that Norrie disease, which is caused by mutations in the Ndp (Norrie disease pseudoglioma) gene located on the X-chromosome, may be linked to the secretion of active Norrin protein from distinct astrocyte subsets and subsequent activation of the Wnt signaling pathway in surrounding cells [58]. Consistent with the involvement of Wnt signaling in CNS patterning [110] and synapse formation [111], patients generally present with blindness. Studies in a mouse model carrying a mutation in exon 2 of the Ndp gene [112], which results in the deletion of 56 amino acids from the N-terminus of the protein, suggest that this is due to disorganization of the ganglion cell layer and loss of the outer plexiform layer in the retina.…”

Axin Family of Scaffolding Proteins in Development: Lessons from C. elegans

“…As a scaffolding protein, Axin facilitates the recruitment of various proteins to regulate gene expression and cytoskeletal dynamics. Through these actions, Axin affects signaling pathway activities, e.g., WNT-β-catenin, JNK (c-Jun N-terminal kinase) and TGF-β (transforming growth factor-beta) (see below for more details), and organization of proteins such as microtubules (reviewed in [40,41]). Previously, it was shown that ectopic Axin expression in cultured cells blocked neuronal differentiation, a process that involved WNT-3a-β-catenin signaling [42].…”

Canonical Wnt-signaling modulates the tempo of dendritic growth of adult-born hippocampal neurons

“…Wnt-dependent signaling pathways serve pleiotropic functions in embryonic and adult neurogenesis. While canonical Wnt-signaling has been primarily linked to early neurodevelopmental processes such as precursor proliferation and fate determination (Chenn & Walsh, 2002, Hirabayashi, Itoh et al, 2004, Kuwabara et al, 2009, Lie et al, 2005, Woodhead, Mutch et al, 2006, non-canonical Wnt-signaling pathways are considered the main drivers of neural circuit formation and plasticity (He, Liao et al, 2018, McLeod & Salinas, 2018, Salinas, 2012. We demonstrate that dendritogenesis of adult-born dentate granule neurons is dependent on canonical Wnt/-catenin-signaling, which complements recent evidence that canonical Wnt/-catenin-signaling contributes to neuronal maturation and circuit formation in embryonic neurodevelopment (Martin et al, 2018, Ramos-Fernandez, Tapia-Rojas et al, 2019, Viale, Song et al, 2019.…”