Celsr1 adhesive interactions mediate the asymmetric organization of planar polarity complexes

Stahley, Sara N.; Basta, Lena P.; Sharan, Rishabh; Devenport, Danelle

doi:10.7554/elife.62097

Cited by 39 publications

(52 citation statements)

References 72 publications

(91 reference statements)

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“…However, another PCP protein, Frizzled7, has also been shown to tune cadherin adhesion during Xenopus CE, but bi-fluorescence complementation experiments suggested Frizzled7 inhibits cis-clustering ( Kraft et al, 2012 ). Adding additional complexity is the recent finding that the PCP protein Celsr1, itself an atypical cadherin, not only forms adhesive trans-dimers but also tunes PCP signaling ( Stahley et al, 2021 ). Unraveling the relationship between PCP, cadherins, and cell adhesion is thus an important challenge for future work.…”

Section: Discussionmentioning

confidence: 99%

Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation

Huebner

Malmi-Kakkada

Sarıkaya

et al. 2021

eLife

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Morphogenesis is governed by the interplay of molecular signals and mechanical forces across multiple length scales. The last decade has seen tremendous advances in our understanding of the dynamics of protein localization and turnover at sub-cellular length scales, and at the other end of the spectrum, of mechanics at tissue-level length scales. Integrating the two remains a challenge, however, because we lack a detailed understanding of the subcellular patterns of mechanical properties of cells within tissues. Here, in the context of the elongating body axis of Xenopus embryos, we combine tools from cell biology and physics to demonstrate that individual cell-cell junctions display finely-patterned local mechanical heterogeneity along their length. We show that such local mechanical patterning is essential for the cell movements of convergent extension and is imparted by locally patterned clustering of a classical cadherin. Finally, the patterning of cadherins and thus local mechanics along cell-cell junctions are controlled by Planar Cell Polarity signaling, a key genetic module for CE that is mutated in diverse human birth defects.

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Section: Discussionmentioning

confidence: 99%

Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation

Huebner

Malmi-Kakkada

Sarıkaya

et al. 2021

eLife

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“…Persistent sfGFP-Vangl2 enrichment was observed along anterior membrane domains (Supplementary Movie 1), supporting evidence from multiple Drosophila, Xenopus and mouse studies (predominantly using exogenous reporters) that PCP components concentrate into potential "signalosomes" on the cell membrane. 9,16,20,28,[32][33][34][35] In Xenopus, exogenous Vangl2 and Prickle reporters accumulate with actomyosin at shrinking neuroepithelial cell junctions 9 and, in mesodermal cells undergoing convergence and extension movements, Prickle2 colocalizes with the LifeAct filamentous actin reporter. 35,36 These observations suggest that Vangl2/PCP directly influences cytoskeletal reorganization.…”

Section: Resultsmentioning

confidence: 99%

Live imaging and conditional disruption of native vertebrate planar cell polarity

Jussila¹,

Boswell²,

Ciruna³

2021

Preprint

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Tissue-wide coordination of polarized cytoskeletal organization and cell behaviour, critical for organ morphogenesis and tumour progression, is controlled by asymmetric membrane localization of non-canonical Wnt/planar cell polarity (PCP) signalling components. Understanding the dynamic regulation of PCP thus requires visualization of these core proteins. In vertebrates, immunohistochemical studies have provided snapshots of PCP within tissues while exogenous, fluorescently-tagged reporters have been introduced for live imaging of cell polarity. However, the functionality and spatiotemporal relevance of static and exogenous PCP readouts remain uncertain. Here we fluorescently tag an endogenous core PCP component, Vangl2, in zebrafish. We report on the authentic regulation of vertebrate PCP, through live imaging of this native sfGFP-Vangl2 protein during embryogenesis. We couple sfGFP-Vangl2 with conditional zGrad GFP-nanobody degradation methodologies for tissue-specific interrogation of PCP function. Together, our studies provide crucial insights into the establishment and maintenance of vertebrate PCP and create a powerful experimental paradigm for future investigations.

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“…Cadherins commonly form puncta, though the causes and functions of this organization vary [47][48][49] . For example, Flamingo (or mammalian Celsr1), an atypical cadherin and central component of the core planar cell polarity pathway, is stabilized by clustering, and this clustering is important for its planar polarization [50][51][52] . In future work, it will be important to determine how Fat2 assembles in puncta, and whether this local clustering is important for its polarization to trailing edges or its effect on the organization of leading edges.…”

Section: Discussionmentioning

confidence: 99%

Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration

Williams

Donoughe

Munro

et al. 2022

Preprint

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For a group of cells to migrate together, each cell must couple the polarity of its own migratory machinery with that of the other cells in the migrating group. Although collective cell migrations are common in animal development, it is not understood how protrusions are coherently polarized within groups of migrating epithelial cells. We address this problem in the collective migration of the Drosophila melanogaster follicular epithelial cells, demonstrating that the atypical cadherin Fat2 relays polarity information between neighboring cells, causing them to align their lamellipodia and migrate together. Fat2 localizes the WAVE complex to the leading edge of each cell, where the WAVE complex builds polarized lamellipodia. In Fat2's absence, the WAVE complex becomes enriched at fluctuating positions around the cell perimeter, resulting in short-lived and spatially disordered protrusive regions, ultimately causing collective migration to fail. In wild-type tissue, Fat2 puncta along the trailing edge of each cell concentrate the WAVE complex in corresponding puncta just across the cell-cell interface, restricting WAVE complex activity and protrusions to one stable leading edge. In summary, migrating cells couple their protrusive activity to that of their neighbors using a polarized transmembrane cue. We propose that this mechanism enables the tissue to achieve persistent, days-long directed migration.

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Celsr1 adhesive interactions mediate the asymmetric organization of planar polarity complexes

Cited by 39 publications

References 72 publications

Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation

Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation

Live imaging and conditional disruption of native vertebrate planar cell polarity

Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration

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