The Tricellular Junction Protein Sidekick Regulates Vertex Dynamics to Promote Bicellular Junction Extension

Uechi, Hiroyuki; Kuranaga, Erina

doi:10.1016/j.devcel.2019.06.017

Cited by 49 publications

(74 citation statements)

References 57 publications

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“…Indeed, all of these predictions are strongly supported by the rates of contracting and growing cell interfaces (Fig 4C and Fig 2,3 in S2 File): During the last 10 minutes of contraction, the average contracting cell junction nearly triples its contraction rate, while the growing junction reduces its rate by~30% over the same duration. The average junction contraction and growth rates during these periods agree with previous reports [43,44]. Also consistent with previous studies is the strong alignment of contracting junctions with the short axis of the embryo, and, though to a lesser extent, of growing junctions with the long axis ( Fig 4E.i,ii) [45].…”

Section: Statistical Properties Of Intercalary Motifssupporting

confidence: 92%

Template-based mapping of dynamic motifs in tissue morphogenesis

2020

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Tissue morphogenesis relies on repeated use of dynamic behaviors at the levels of intracellular structures, individual cells, and cell groups. Rapidly accumulating live imaging datasets make it increasingly important to formalize and automate the task of mapping recurrent dynamic behaviors (motifs), as it is done in speech recognition and other data mining applications. Here, we present a "template-based search" approach for accurate mapping of sub-to multi-cellular morphogenetic motifs using a time series data mining framework. We formulated the task of motif mapping as a subsequence matching problem and solved it using dynamic time warping, while relying on high throughput graph-theoretic algorithms for efficient exploration of the search space. This formulation allows our algorithm to accurately identify the complete duration of each instance and automatically label different stages throughout its progress, such as cell cycle phases during cell division. To illustrate our approach, we mapped cell intercalations during germband extension in the early Drosophila embryo. Our framework enabled statistical analysis of intercalary cell behaviors in wild-type and mutant embryos, comparison of temporal dynamics in contracting and growing junctions in different genotypes, and the identification of a novel mode of iterative cell intercalation. Our formulation of tissue morphogenesis using time series opens new avenues for systematic decomposition of tissue morphogenesis.

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Section: Statistical Properties Of Intercalary Motifssupporting

confidence: 92%

Template-based mapping of dynamic motifs in tissue morphogenesis

2020

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“…Since each cell in the ectoderm divides at least twice after the end of GBE, this is likely to account for restoring isotropic apical shapes to cells in the embryonic epithelium. Despite the viability of sdk mutants, two studies published while this article was under review report cell intercalation defects in sdk mutants in three other Drosophila tissues: the embryonic trachea and the pupal retina [56] and the genitalia disc [57]. This indicates that a role of Sdk in cell rearrangements might be widespread in Drosophila epithelia.…”

Section: Discussionmentioning

confidence: 99%

The tricellular vertex-specific adhesion molecule Sidekick facilitates polarised cell intercalation during Drosophila axis extension

et al. 2019

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In epithelia, tricellular vertices are emerging as important sites for the regulation of epithelial integrity and function. Compared to bicellular contacts, however, much less is known. In particular, resident proteins at tricellular vertices were identified only at occluding junctions, with none known at adherens junctions (AJs). In a previous study, we discovered that in Drosophila embryos, the adhesion molecule Sidekick (Sdk), well-known in invertebrates and vertebrates for its role in the visual system, localises at tricellular vertices at the level of AJs. Here, we survey a wide range of Drosophila epithelia and establish that Sdk is a resident protein at tricellular AJs (tAJs), the first of its kind. Clonal analysis showed that two cells, rather than three cells, contributing Sdk are sufficient for tAJ localisation. Super-resolution imaging using structured illumination reveals that Sdk proteins form string-like structures at vertices. Postulating that Sdk may have a role in epithelia where AJs are actively remodelled, we analysed the phenotype of sdk null mutant embryos during Drosophila axis extension using quantitative methods. We find that apical cell shapes are abnormal in sdk mutants, suggesting a defect in tissue remodelling during convergence and extension. Moreover, adhesion at apical vertices is compromised in rearranging cells, with apical tears in the cortex forming and persisting throughout axis extension, especially at the centres of rosettes. Finally, we show that polarised cell intercalation is decreased in sdk mutants. Mathematical modelling of the cell behaviours supports the notion that the T1 transitions of polarised cell intercalation are delayed in sdk mutants, in particular in rosettes. We propose that this delay, in combination with a change in the mechanical properties of the converging and extending tissue, causes the abnormal apical cell shapes in sdk mutant embryos.

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“…In an earlier report on the Sdk-null mutant (Nguyen et al, 1997), other mysterious phenotypes, such as fused ommatidia, disrupted bristle pattern, and missing pigment cells were also noticed, in addition to photoreceptor abnormalities. In the absence of Sdk, disorganization was also seen in several other epithelia such as the epidermis, tracheae, and male genitalia (Finegan et al, 2019;Letizia et al, 2019;Uechi and Kuranaga, 2019). Detailed analyses of these defects revealed that Sdk proteins at tAJs control dynamic junctional rearrangements in developing epithelia.…”

Section: Sdk In Drosophila Photoreceptors and Tricellular Adherens Jumentioning

confidence: 99%

“…(B) Epithelial cells build adhesive contacts along their apical-basal axes, both at the bicellular adherens junctions (bAJs) and at the tricellular adherens junctions (tAJs) in Drosophila. Sdk is highly concentrated at tAJs which are at the vertex of three mature epithelial cells (Cell-1, Cell-2, and Cell-3) whereas E-cadherin participates in forming bAJ (Finegan et al, 2019;Letizia et al, 2019;Uechi and Kuranaga, 2019) (B). (C) At tAJs, the Sdk protein functionally links to Polychaetoid (Figure 3) and Canoe, modulates dynamically E-cadherin by associating with actomyosin cytoskeletons during development, and maintains epithelial sheets.…”

Section: Sdks In Vertebrate Neural Circuitsmentioning

confidence: 99%

Structure and Functions of Sidekicks

Yamagata

2020

Front. Mol. Neurosci.

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Many of the immunoglobulin superfamily (IgSF) molecules play pivotal roles in cell communication. The Sidekick (Sdk) gene, first described in Drosophila, encodes the single-pass transmembrane protein, Sdk, which is one of the largest among IgSF membrane proteins. Sdk first appeared in multicellular animals during the Precambrian age and later evolved to Sdk1 and Sdk2 in vertebrates by gene duplication. In flies, a single Sdk is involved in positioning photoreceptor neurons and their axons in the visual system and is responsible for dynamically rearranging cell shapes by strictly populating tricellular adherens junctions in epithelia. In vertebrates, Sdk1 and Sdk2 are expressed by unique sets of cell types and distinctively participate in the formation and/or maintenance of neural circuits in the retina, indicating that they are determinants of synaptic specificity. These functions are mediated by specific homophilic binding of their ectodomains and by intracellular association with PDZ scaffold proteins. Recent human genetic studies as well as animal experiments implicate that Sdk genes may influence various neurodevelopmental and psychiatric disorders, such as autism spectrum disorders, attention-deficit hyperactivity disorder, addiction, and depression. The gigantic Sdk1 gene is susceptible to erratic gene rearrangements or mutations in both somatic and germ-line cells, potentially contributing to neurological disorders and some types of cancers. This review summarizes what is known about the structure and roles of Sdks.

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The Tricellular Junction Protein Sidekick Regulates Vertex Dynamics to Promote Bicellular Junction Extension

Cited by 49 publications

References 57 publications

Template-based mapping of dynamic motifs in tissue morphogenesis

Template-based mapping of dynamic motifs in tissue morphogenesis

The tricellular vertex-specific adhesion molecule Sidekick facilitates polarised cell intercalation during Drosophila axis extension

Structure and Functions of Sidekicks

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