Abstract:Highlights d Asymmetric expression of a single Toll receptor leads to Myo-II polarization d The adhesion GPCR Cirl binds to Toll-8 mediating Toll-8induced Myo-II polarization d Toll-8 boundaries generate a Cirl interfacial asymmetry that can polarize Myo-II d Differences in Toll-8 levels lead to interdependent Toll-8 and Cirl planar polarity
“…Recent experimental evidence suggests that cells in the Drosophila germ-band enrich cortical Myosin II using a neighbour ‘identity’-sensing mechanism [ 17 , 57 – 59 ]. In particular, cells have been found to locally recruit Myosin in response to the genetic identity of their neighbours, specified by the asymmetric localisation of cell surface receptors between the apposed cortices in a bicellular junction [ 59 ].…”
Section: Resultsmentioning
confidence: 99%
“…Recent experimental evidence suggests that cells in the Drosophila germ-band enrich cortical Myosin II using a neighbour 'identity'-sensing mechanism [17,[57][58][59]. In particular, cells have been found to locally recruit Myosin in response to the genetic identity of their neighbours, specified by the asymmetric localisation of cell surface receptors between the apposed PLOS COMPUTATIONAL BIOLOGY cortices in a bicellular junction [59]. We mimic this mechanism by making the local level of active cortical contractility dependent on the identity of the cells with which these surface receptors are shared.…”
Section: Implementing Active Neighbour Exchanges In the Apposed-cortex Adhesion Modelmentioning
Cell intercalation is a key cell behaviour of morphogenesis and wound healing, where local cell neighbour exchanges can cause dramatic tissue deformations such as body axis extension. Substantial experimental work has identified the key molecular players facilitating intercalation, but there remains a lack of consensus and understanding of their physical roles. Existing biophysical models that represent cell-cell contacts with single edges cannot study cell neighbour exchange as a continuous process, where neighbouring cell cortices must uncouple. Here, we develop an Apposed-Cortex Adhesion Model (ACAM) to understand active cell intercalation behaviours in the context of a 2D epithelial tissue. The junctional actomyosin cortex of every cell is modelled as a continuous viscoelastic rope-loop, explicitly representing cortices facing each other at bicellular junctions and the adhesion molecules that couple them. The model parameters relate directly to the properties of the key subcellular players that drive dynamics, providing a multi-scale understanding of cell behaviours. We show that active cell neighbour exchanges can be driven by purely junctional mechanisms. Active contractility and cortical turnover in a single bicellular junction are sufficient to shrink and remove a junction. Next, a new, orthogonal junction extends passively. The ACAM reveals how the turnover of adhesion molecules regulates tension transmission and junction deformation rates by controlling slippage between apposed cell cortices. The model additionally predicts that rosettes, which form when a vertex becomes common to many cells, are more likely to occur in actively intercalating tissues with strong friction from adhesion molecules.
“…Recent experimental evidence suggests that cells in the Drosophila germ-band enrich cortical Myosin II using a neighbour ‘identity’-sensing mechanism [ 17 , 57 – 59 ]. In particular, cells have been found to locally recruit Myosin in response to the genetic identity of their neighbours, specified by the asymmetric localisation of cell surface receptors between the apposed cortices in a bicellular junction [ 59 ].…”
Section: Resultsmentioning
confidence: 99%
“…Recent experimental evidence suggests that cells in the Drosophila germ-band enrich cortical Myosin II using a neighbour 'identity'-sensing mechanism [17,[57][58][59]. In particular, cells have been found to locally recruit Myosin in response to the genetic identity of their neighbours, specified by the asymmetric localisation of cell surface receptors between the apposed PLOS COMPUTATIONAL BIOLOGY cortices in a bicellular junction [59]. We mimic this mechanism by making the local level of active cortical contractility dependent on the identity of the cells with which these surface receptors are shared.…”
Section: Implementing Active Neighbour Exchanges In the Apposed-cortex Adhesion Modelmentioning
Cell intercalation is a key cell behaviour of morphogenesis and wound healing, where local cell neighbour exchanges can cause dramatic tissue deformations such as body axis extension. Substantial experimental work has identified the key molecular players facilitating intercalation, but there remains a lack of consensus and understanding of their physical roles. Existing biophysical models that represent cell-cell contacts with single edges cannot study cell neighbour exchange as a continuous process, where neighbouring cell cortices must uncouple. Here, we develop an Apposed-Cortex Adhesion Model (ACAM) to understand active cell intercalation behaviours in the context of a 2D epithelial tissue. The junctional actomyosin cortex of every cell is modelled as a continuous viscoelastic rope-loop, explicitly representing cortices facing each other at bicellular junctions and the adhesion molecules that couple them. The model parameters relate directly to the properties of the key subcellular players that drive dynamics, providing a multi-scale understanding of cell behaviours. We show that active cell neighbour exchanges can be driven by purely junctional mechanisms. Active contractility and cortical turnover in a single bicellular junction are sufficient to shrink and remove a junction. Next, a new, orthogonal junction extends passively. The ACAM reveals how the turnover of adhesion molecules regulates tension transmission and junction deformation rates by controlling slippage between apposed cell cortices. The model additionally predicts that rosettes, which form when a vertex becomes common to many cells, are more likely to occur in actively intercalating tissues with strong friction from adhesion molecules.
“…In an alternative model, each boundary of the TLR expression domain may planar polarize cells independent of interaction with other TLRs. This model is supported by detailed analyses of Toll-8 [ 6 ] that demonstrate, among other findings, that ectopic Toll-8 expression in the absence of endogenous Toll-2, 6, 8 is sufficient to induce recruitment of Myo-II at the border of the ectopic expression domain, which suggests that the Myo-II enrichment on cell junctions is established solely by the differential expression level of Toll-8 and does not require interaction with other TLRs. Figure 3.…”
Section: Introductionmentioning
confidence: 64%
“…In Toll-2 null mutants, planar polarity specifically at the border of the Toll-2 expression domain is lost, but that of the AP edges inside the domain is unaffected [ 12 ]. Similarly, in embryos with depleted Toll-2, 6 , and 7 , where endogenous Toll-8 alone is expressed, Myo-II remains accumulated along the stripes at the border of Toll-8 expression domains [ 6 ]. Thirdly, after the completion of a series of oriented cell intercalations, some stripes of Myo-II enrichment disappear [ 70 ].…”
Section: Introductionmentioning
confidence: 99%
“…Ectopic Toll-8 expression in mosaic clones in wing discs sorts out cells from surrounding wild type cells, and cell sorting is accompanied by Myo-II accumulation at clone borders [ 6 , 72 ]. Unlike Toll-2, which requires its intracellular domain to planar polarize Myo-II and Par-3, Toll-8 does not require its intracellular domain for Myo-II recruitment at the differential expression border.…”
Signal transduction by the Toll-like receptors (TLRs) is conserved and essential for innate immunity in metazoans. The founding member of the TLR family,
Drosophila
Toll-1, was initially identified for its role in dorsoventral axis formation in early embryogenesis. The
Drosophila
genome encodes nine TLRs that display dynamic expression patterns during development, suggesting their involvement in tissue morphogenesis and homeostasis. Recent progress on the developmental functions of TLRs beyond dorsoventral patterning has revealed not only their diverse functions in various biological processes, but also unprecedented molecular mechanisms in directly regulating cell mechanics and cell-cell recognition independent of the canonical signal transduction pathway involving transcriptional regulation of target genes. In this review, I feature and discuss the non-immune functions of TLRs in the control of epithelial tissue homeostasis, tissue morphogenesis, and cell-cell recognition between cell populations with different cell identities.
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