Non-canonical WNT5A-ROR signaling: New perspectives on an ancient developmental pathway

Current topics in developmental biology/Current Topics in Developmental Biology, Год журнала: 2023, Номер unknown, С. 195 - 227

Опубликована: Янв. 1, 2023

Язык: Английский

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Wnt7b acts in concert with Wnt5a to regulate tissue elongation and planar cell polarity via noncanonical Wnt signaling

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(35)

Опубликована: Авг. 22, 2024

Intercellular signaling mediated by evolutionarily conserved planar cell polarity (PCP) proteins aligns along the tissue plane and drives polarized behaviors during morphogenesis. Accumulating evidence indicates that vertebrate PCP pathway is regulated noncanonical, β-catenin-independent Wnt signaling; however, components mechanisms are incompletely understood. In mouse hearing organ, both noncanonical (ncWnt) required in developing auditory sensory epithelium to control cochlear duct elongation of resident hair cells (HCs), including shape orientation stereociliary bundle essential for sound detection. We have recently discovered a Wnt/G-protein/PI3K coordinates HC intercellular signaling. Here, we identify Wnt7b as ncWnt ligand acting concert with Wnt5a promote diverse developmental processes. cochlea, redundantly coiling elongation, polarity, asymmetric localization core Fzd6 Dvl2. Mechanistically, Wnt5a/Wnt7b-mediated promotes membrane recruitment Daple, nonreceptor guanine nucleotide exchange factor Gαi, activates PI3K/AKT ERK signaling, which localization. Thus, pathways distinct mutant phenotypes components, suggesting they act separate, parallel nonoverlapping functions NcWnt reinforces regulating trafficking PCP-specific Frizzled receptors.

Язык: Английский

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Endocytosis of Wnt ligands from surrounding epithelial cells positions microtubule nucleation sites at dendrite branch points

PLoS Biology, Год журнала: 2025, Номер 23(1), С. e3002973 - e3002973

Опубликована: Янв. 6, 2025

Microtubule nucleation is important for microtubule organization in dendrites and neuronal injury responses. The core protein, γTubulin (γTub), localized to dendrite branch points Drosophila sensory neurons by Wnt receptors scaffolding proteins on endosomes. However, whether ligands are unknown. We found that secretion from epithelial cells was required γTub localization points. Using RNAi mutant approaches, we demonstrated Wnt4 wntD both position γTub. Moreover, injury-induced increases dynamics cells. Overexpression of Wnts increased the same extent as axon indicating surrounding have an instructive role nucleation. To determine how concentrate at points, tested endocytosis restricted specific regions dendrites. Markers clathrin-mediated puncta Behavior these sensitive inhibition suggesting they represented endocytic sites. In addition previously described colocalization scaffolds with Rab5 endosomes, identified a separate set signaling colocalized clathrin protein recruitment reduced RNAi, up-regulation reduction. propose sites results local generation nucleating

Язык: Английский

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Planar cell polarity coordination in a cnidarian embryo provides clues to animal body axis evolution

Опубликована: Янв. 28, 2025

Body axis specification is a crucial event in animal embryogenesis and was an essential evolutionary innovation for founding the kingdom. It involves two distinct components that coordinate to establish spatial organisation of embryo: initiation cascades regionalised gene expression orientation morphogenetic processes such as body elongation. Intense interest first component has revealed Wnt/β-catenin signalling ancestrally responsible initiating regional expression, but origin oriented morphogenesis received little attention. Here, by addressing cell morphological basis development embryos cnidarian Clytia hemisphaerica, we have uncovered simple likely ancestral coordination mechanism between directed morphogenesis. We show ligand Wnt3, known initiate oral via localised pathway activation, also key β-catenin-independent role globally orienting planar polarity (PCP) direct along oral-aboral axis. This PCP occurs steps: local Wnt3 global propagation conserved core protein interactions From these findings propose novel scenarios PCP-driven symmetry-breaking underlying emergence plan.

Язык: Английский

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Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 11, 2025

Convergent extension (CE) is a universal morphogenetic engine that promotes polarized tissue extension. In vertebrates, CE regulated by non-canonical Wnt ligands signaling through "core" proteins of the planar cell polarity (PCP) pathway, including cytoplasmic protein Dishevelled (Dvl), receptor Frizzled (Fz) and tetraspan Van gogh-like (Vangl). PCP was discovered in Drosophila to coordinate plane static epithelium, but does not regulate flies. Existing evidence suggests adopting for might be vertebrate-specific adaptation with incorporation new regulators. Herein we use Xenopus investigate Dact1, chordate-specific protein. Dact1 induces Dvl form oligomers dissociate from Vangl, stay attached Fz as signalosome-like clusters co-aggregate into patches upon induction. Functionally, antagonizes synergizes wild-type its oligomerization-defective mutants. We propose that, promoting oligomerization, couples binding partner switch cluster formation initiate during vertebrate CE. The action morphogenesis remains unclear. Here, authors find oligomerization couple Vangl cluster.

Язык: Английский

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