Planar Polarity: Converting a Morphogen Gradient into Cellular Polarity

Collu, Giovanna M.; Mlodzik, Marek

doi:10.1016/j.cub.2015.03.011

Cited by 8 publications

(11 citation statements)

References 20 publications

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“…A core mechanism by which Wnt-Fz/PCP signaling polarizes epithelial cells is the polarized distribution of different Wnt-Fz/PCP components along the polarization axis (Collu and Mlodzik, 2015). While this is well documented in epithelial cells, it is less clear whether there is any polarized subcellular distribution of Wnt-Fz/PCP components in mesenchymal cells (Roszko et al, 2015; Jussila and Ciruna, 2017).…”

Section: Discussionmentioning

confidence: 99%

Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

Čapek

Smutny

Tichy

et al. 2019

eLife

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Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.

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Section: Discussionmentioning

confidence: 99%

Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

Čapek

Smutny

Tichy

et al. 2019

eLife

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“…On the other hand, conclusive work in Drosophila demonstrated that the DEP domain of Dsh is responsible for the other well-described function of Dsh, which is in the Wnt/planar cell polarity (PCP) pathway. The Wnt/PCP pathway is a molecular mechanism that controls asymmetric localization and the maintenance of polarity in the epithelial sheet (for a review, see reference 11 ). The Dsh DEP domain is required for the association of Dsh with the membrane, an event that underlies the asymmetric subcellular distribution of PCP proteins and a functional Wnt/PCP pathway ( 9 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

The N-Terminal Part of the Dishevelled DEP Domain Is Required for Wnt/β-Catenin Signaling in Mammalian Cells

Paclíková

Bernatík

Radaszkiewicz

et al. 2017

Molecular and Cellular Biology

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Dishevelled (DVL) proteins are key mediators of the Wnt/β-catenin signaling pathway. All DVL proteins contain three conserved domains: DIX, PDZ, and DEP. There is a consensus in the field that the DIX domain is critical for Wnt/β-catenin signaling, but contradictory evidence regarding the function of the DEP domain exists. It has been difficult, until recently, to test the importance of the DEP domain rigorously because of the interference with endogenous DVL, expressed in all Wnt-responsive cell lines. In this study, we took advantage of DVL knockout (DVL1/DVL2/DVL3 triple knockout) cells fully deficient in Wnt3a-induced signaling events and performed a series of rescue experiments. Using these complementation assays, we analyzed the role of individual DVL isoforms. Further domain mapping of DVL1 showed that both the DVL1 DEP domain and especially its N-terminal region are required and sufficient for Wnt3a-induced phosphorylation of LRP6 and TopFlash reporter activation. On the contrary, multiple DEP domain mutants deficient in the planar cell polarity (PCP) pathway could fully rescue the Wnt3a response. This study provides conclusive evidence that the DVL DEP domain is essential for Wnt/β-catenin signaling in mammalian cells and establishes an experimental system suitable for further functional testing of DVL.

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“…Gradients of Daschous (Ds) and Fourjointed (Fj) have also been proposed to orient planar polarity in the wing (reviewed in [50]), although Ds uniform expression rescues the PCP defect of ds(-) [51] demonstrating that Ds gradient per se is not required f o r P C P ( t o m y k n o w l e d g e t h e equivalent experiment with Fj has not been reported). Nonetheless the Fz homophobic signal can be reconciled with the proximal-distal bias being established by any gradient provided that the said gradient affects the stability of the Fz-Fmi interaction.…”

Section: Wg/wnt (And Other) Gradient(s)mentioning

confidence: 99%

Planar Cell Polarity: The Frizzled Homophobic Signal

Gomes¹

2019

Preprint

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The cell’s capacity to integrate and respond to spatial information is a crucial feature of morphogenesis and development. The Planar Cell Polarity (PCP) pathway is a signaling mechanism, widely conserved across metazoans, providing spatial orientation along the plane of an epithelium in morphogenic processes ranging from insect wing patterning to mammalian cochleae. Although the core genes involved in the PCP pathway have been molecularly identified in the 1990s, the PCP signaling mechanism remains controversial. In this article I discuss the main players and previous models of PCP signaling reported in the literature, and propose a new model. According to it PCP is established through an homophobic signal by transmembrane protein Frizzled (Fz): 1) a Fz signal in one cell repeals Fz itself in the adjacent cell, thereby generating symmetry breaking; 2) the instructive PCP signal is conveyed through Fz interaction with atypical cadherin Flamingo (Fmi). More broadly, homophobic signaling may represent a novel mechanism for cell-cell signaling of spatial information through modulation of cell adhesion rather than canonical ligand-receptor binding.

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Planar Polarity: Converting a Morphogen Gradient into Cellular Polarity

Cited by 8 publications

References 20 publications

Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

The N-Terminal Part of the Dishevelled DEP Domain Is Required for Wnt/β-Catenin Signaling in Mammalian Cells

Planar Cell Polarity: The Frizzled Homophobic Signal

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