How do the Fat–Dachsous and core planar polarity pathways act together and independently to coordinate polarized cell behaviours?

Strutt, Helen; Strutt, David

doi:10.1098/rsob.200356

Cited by 34 publications

(42 citation statements)

References 188 publications

(500 reference statements)

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“…We decided to test whether regulation of Trc by CCM3-GCKIII was tissue-specific, or instead might be a general feature of Trc regulation. To do so, we turned to the Drosophila wing, a system widely used for studying developmental signaling pathways and planar cell polarity [42][43][44][45][46][47] .…”

Section: Resultsmentioning

confidence: 99%

Furry is a component of the CCM3-GCKIII signaling pathway

Antwi-Adjei¹,

Burguete²,

Ghabrial³

2021

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Aim: Mutations in 3 genes encoding proteins of the Cerebral Cavernous Malformations (CCM) ternary complex cause autosomal dominant cerebral vascular disease. Targets of CCM complex regulation have been identified; however, the molecular mechanisms connecting CCM3 to these downstream effectors remain elusive. We aim to determine the mechanism of CCM3 action by using a Drosophila model to elucidate the signaling pathway downstream of CCM3. Previously, we showed that CCM3 and its binding partner, Germinal Center Kinase 3, are required in tracheal terminal cells to prevent tube morphogenesis defects. Further, we established that GCKIII phosphorylates and directly activates a downstream kinase, Tricornered (Drosophila STK38/38L ortholog). Here we aim to test whether Tricornered-associated scaffolding protein, Furry, is required for CCM3-GCKIII signaling. Methods:We utilized the FRT-FLP system to generate genetic mosaic Drosophila larvae and adults. Mitotic recombination was induced in embryos (trachea) or larvae (wing disc). The animals were heterozygous for the gene of interest (ccm3 or furry), but after recombination, homozygous mutant daughter cells were produced. In addition, the GAL4-UAS system was used to express dominant negative GCKIII in wing disc cells. Mutant cells were analyzed by brightfield and/or fluorescent microscopy.Results: We find that wing cells mutant for ccm3, or expressing dominant negative GCKIII, produce wing hair defects characteristic of mutations in tricornered and furry. Likewise, tracheal terminal cells mutant for furry produce tube dilation defects characteristic of cells mutant for ccm3 or GCKIII. Conclusion:CCM3 and GCKIII act upstream of Furry-Tricornered, suggesting the conservation from yeast of a Hippo-like signaling pathway that regulates morphogenesis. We speculate that some combination of Furry/Furrylike and STK38/38L are therefore likely to act downstream of CCM3 in endothelial cells.

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Section: Resultsmentioning

confidence: 99%

Furry is a component of the CCM3-GCKIII signaling pathway

Antwi-Adjei¹,

Burguete²,

Ghabrial³

2021

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“…Moreover, PCP systems are not independent from each other and their connections are tightly regulated in vivo. A case study is the connection between the core PCP and the Ft/Ds PCP [88], which has been puzzling to understand since they are connected in some Drosophila tissue such as the wing and the eye, but independent in other tissues like the abdomen [89]. These contradicting observations can now be reconciled.…”

Section: Discussionmentioning

confidence: 99%

In search of conserved principles of planar cell polarization

Lavalou

Lecuit

2022

Current Opinion in Genetics & Development

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The making of an embryo and its internal organs entails the spatial coordination of cellular activities. This manifests during tissue morphogenesis as cells change shape, rearrange and divide along preferential axis and during cell differentiation. Cells live in a polarized field and respond to it by polarizing their cellular activities in the plane of the tissue by a phenomenon called planar cell polarization. This phenomenon is ubiquitous in animals and depends on a few conserved planar cell polarity (PCP) pathways. All PCP pathways share two essential characteristics: the existence of local interactions between protein complexes present at the cell surface leading to their asymmetric distribution within cells; a supracellular graded cue that aligns these cellular asymmetries at the tissue level. Here, we discuss the potential common principles of planar cell polarization by comparing the local and global mechanisms employed by the different PCP pathways identified so far. The focus of the review is on the logic of the system rather than the molecules per se.

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“…Although this is similarly important for the development and functions of epithelia, we will not further elaborate on this aspect here, and the reader is referred to more recent comprehensive reviews on this topic. [28][29] Epithelia also play an essential role in tissue and organ morphogenesis and in shaping the body. This function is made possible by the ease by which epithelial cells modify their shape allowing morphogenetic changes of the whole tissue to occur.…”

Section: Epithelial Cell Polarity and Adhesion Are Crucial For Morphogenesismentioning

confidence: 99%

Reactive oxygen species (ROS) constitute an additional player in regulating epithelial development

Hebbar

Knust

2021

BioEssays

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Reactive oxygen species (ROS) are highly reactive molecules produced in cells. So far, they have mostly been connected to diseases and pathological conditions. More recent results revealed a somewhat unexpected role of ROS in control of developmental processes. In this review, we elaborate on ROS in development, focussing on their connection to epithelial tissue morphogenesis. After briefly summarising unique characteristics of epithelial cells, we present some characteristic features of ROS species, their production and targets, with a focus on proteins important for epithelial development and function. Finally, we provide examples of regulation of epithelial morphogenesis by ROS, and also of developmental genes that regulate the overall redox status. We conclude by discussing future avenues of research that will further elucidate ROS regulation in epithelial development.

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How do the Fat–Dachsous and core planar polarity pathways act together and independently to coordinate polarized cell behaviours?

Cited by 34 publications

References 188 publications

Furry is a component of the CCM3-GCKIII signaling pathway

Furry is a component of the CCM3-GCKIII signaling pathway

In search of conserved principles of planar cell polarization

Reactive oxygen species (ROS) constitute an additional player in regulating epithelial development

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