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The importance of structured noise in the generation of self-organizing tissue patterns through contact-mediated cell-cell signalling.

Cohen M, Baum B, Miodownik M - J R Soc Interface (2010)

Bottom Line: Here, we develop a general model of protrusion-based patterning to analyse the role of noise in this process.By analysing the effects of introducing thresholds required for signal detection in this model of lateral inhibition, our study shows how filopodia-mediated cell-cell communication can generate complex patterns of spots and stripes, which, in the presence of signalling noise, align themselves across a patterning field.Thus, intermittent protrusion-based signalling has the potential to yield robust self-organizing tissue-wide patterns without the need to invoke diffusion-mediated signalling.

View Article: PubMed Central - PubMed

Affiliation: CoMPLEX, University College London, London, UK. m.cohen@ucl.ac.uk

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Sensory organ patterning is driven by signalling between dynamic cellular protrusions. (a) A section of the notum of an adult Drosophila melanogaster fruitfly displays the evenly spaced, grid-like pattern of microchaete bristles that act as mechanosensory organs. Between each bristle are ordinary epithelial cells, each of which expresses a small hair. (b) The development of the pattern of mechanosensory organ precursor cells can be observed in fly pupae. The image shows the apical section of epithelial cells in an area of the notum close to the fly midline, at 14 h after pupae formation. Cells destined to become sensory organs (microchaete bristles) express Neuralized-Gal4, UAS-Moesin-GFP (Neu-GFP). Ubiquitously expressed E-Cadherin-GFP is used to visualize apical cell–cell junctions. (c) Confocal sections reveal the dynamic protrusions (filopodia and lamelopodia) in the basal section of a typical epithelial cell. The cell in this example is imaged through its expression of Neu-GFP. The image shows the position of filopodia at three 100 s intervals, which extend over multiple cell diameters. The arrows highlight the ends of two filopodia that can be observed extending and retracting (mean filopodia lifetime approx. 500 s—data not shown). Scale bars, 10 µm, (c) (i) 0 s, (ii) 100 s, (iii) 200 s.
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RSIF20100488F1: Sensory organ patterning is driven by signalling between dynamic cellular protrusions. (a) A section of the notum of an adult Drosophila melanogaster fruitfly displays the evenly spaced, grid-like pattern of microchaete bristles that act as mechanosensory organs. Between each bristle are ordinary epithelial cells, each of which expresses a small hair. (b) The development of the pattern of mechanosensory organ precursor cells can be observed in fly pupae. The image shows the apical section of epithelial cells in an area of the notum close to the fly midline, at 14 h after pupae formation. Cells destined to become sensory organs (microchaete bristles) express Neuralized-Gal4, UAS-Moesin-GFP (Neu-GFP). Ubiquitously expressed E-Cadherin-GFP is used to visualize apical cell–cell junctions. (c) Confocal sections reveal the dynamic protrusions (filopodia and lamelopodia) in the basal section of a typical epithelial cell. The cell in this example is imaged through its expression of Neu-GFP. The image shows the position of filopodia at three 100 s intervals, which extend over multiple cell diameters. The arrows highlight the ends of two filopodia that can be observed extending and retracting (mean filopodia lifetime approx. 500 s—data not shown). Scale bars, 10 µm, (c) (i) 0 s, (ii) 100 s, (iii) 200 s.

Mentions: The basic principle is that identical cells within a two-dimensional epithelial sheet compete to change state. Moreover, cells undergoing a switch in state inhibit their neighbouring cells from doing so. The result of this competition between cells within an emerging patterned field is, over time, the development of a pattern of spaced differentiated cells within the tissue [20,21]. The organization of the mechanosensory organ precursor cells on the notum of the Drosophila fly is a good example of a pattern generated in this way [22–25]. During this process, membrane-tethered Delta activates Notch signalling in neighbouring cells, inhibiting their ability to express Delta to yield a spaced pattern of mechanosensory (microchaete) bristles [21,22,24,26] (figure 1a,b). The need for cell–cell contact in this type of signalling is a key feature of the lateral inhibition process [22,27,28]. Although lateral inhibition signalling systems have been extensively modelled [21,29–32], by quantitatively comparing the results of simulations and experiments, we recently showed that conventional models of Notch–Delta signalling cannot account for bristle spacing on the Drosophila notum or the gradual refinement of the pattern of bristle precursor cells, which is observed using live imaging over a period of approximately 8 h in the developing fruitfly notum [2]. In fact, the developing bristle pattern is dependent upon Delta–Notch signalling mediated by dynamic, basal actin-based filopodia that induce intermittent cell–cell signalling contacts between non-neighbouring cells (figure 1c). Significantly, these filopodial dynamics generate a type of structured noise that contributes to patterning [2]. We use the terminology structured noise, in this context, to distinguish the intermittent signalling arising from a physical process under the control of individual cells, from more stochastic forms of signal noise, such as that which occurs as a result of variations in interactions between proteins in a signal transduction pathway.Figure 1.


The importance of structured noise in the generation of self-organizing tissue patterns through contact-mediated cell-cell signalling.

Cohen M, Baum B, Miodownik M - J R Soc Interface (2010)

Sensory organ patterning is driven by signalling between dynamic cellular protrusions. (a) A section of the notum of an adult Drosophila melanogaster fruitfly displays the evenly spaced, grid-like pattern of microchaete bristles that act as mechanosensory organs. Between each bristle are ordinary epithelial cells, each of which expresses a small hair. (b) The development of the pattern of mechanosensory organ precursor cells can be observed in fly pupae. The image shows the apical section of epithelial cells in an area of the notum close to the fly midline, at 14 h after pupae formation. Cells destined to become sensory organs (microchaete bristles) express Neuralized-Gal4, UAS-Moesin-GFP (Neu-GFP). Ubiquitously expressed E-Cadherin-GFP is used to visualize apical cell–cell junctions. (c) Confocal sections reveal the dynamic protrusions (filopodia and lamelopodia) in the basal section of a typical epithelial cell. The cell in this example is imaged through its expression of Neu-GFP. The image shows the position of filopodia at three 100 s intervals, which extend over multiple cell diameters. The arrows highlight the ends of two filopodia that can be observed extending and retracting (mean filopodia lifetime approx. 500 s—data not shown). Scale bars, 10 µm, (c) (i) 0 s, (ii) 100 s, (iii) 200 s.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3104346&req=5

RSIF20100488F1: Sensory organ patterning is driven by signalling between dynamic cellular protrusions. (a) A section of the notum of an adult Drosophila melanogaster fruitfly displays the evenly spaced, grid-like pattern of microchaete bristles that act as mechanosensory organs. Between each bristle are ordinary epithelial cells, each of which expresses a small hair. (b) The development of the pattern of mechanosensory organ precursor cells can be observed in fly pupae. The image shows the apical section of epithelial cells in an area of the notum close to the fly midline, at 14 h after pupae formation. Cells destined to become sensory organs (microchaete bristles) express Neuralized-Gal4, UAS-Moesin-GFP (Neu-GFP). Ubiquitously expressed E-Cadherin-GFP is used to visualize apical cell–cell junctions. (c) Confocal sections reveal the dynamic protrusions (filopodia and lamelopodia) in the basal section of a typical epithelial cell. The cell in this example is imaged through its expression of Neu-GFP. The image shows the position of filopodia at three 100 s intervals, which extend over multiple cell diameters. The arrows highlight the ends of two filopodia that can be observed extending and retracting (mean filopodia lifetime approx. 500 s—data not shown). Scale bars, 10 µm, (c) (i) 0 s, (ii) 100 s, (iii) 200 s.
Mentions: The basic principle is that identical cells within a two-dimensional epithelial sheet compete to change state. Moreover, cells undergoing a switch in state inhibit their neighbouring cells from doing so. The result of this competition between cells within an emerging patterned field is, over time, the development of a pattern of spaced differentiated cells within the tissue [20,21]. The organization of the mechanosensory organ precursor cells on the notum of the Drosophila fly is a good example of a pattern generated in this way [22–25]. During this process, membrane-tethered Delta activates Notch signalling in neighbouring cells, inhibiting their ability to express Delta to yield a spaced pattern of mechanosensory (microchaete) bristles [21,22,24,26] (figure 1a,b). The need for cell–cell contact in this type of signalling is a key feature of the lateral inhibition process [22,27,28]. Although lateral inhibition signalling systems have been extensively modelled [21,29–32], by quantitatively comparing the results of simulations and experiments, we recently showed that conventional models of Notch–Delta signalling cannot account for bristle spacing on the Drosophila notum or the gradual refinement of the pattern of bristle precursor cells, which is observed using live imaging over a period of approximately 8 h in the developing fruitfly notum [2]. In fact, the developing bristle pattern is dependent upon Delta–Notch signalling mediated by dynamic, basal actin-based filopodia that induce intermittent cell–cell signalling contacts between non-neighbouring cells (figure 1c). Significantly, these filopodial dynamics generate a type of structured noise that contributes to patterning [2]. We use the terminology structured noise, in this context, to distinguish the intermittent signalling arising from a physical process under the control of individual cells, from more stochastic forms of signal noise, such as that which occurs as a result of variations in interactions between proteins in a signal transduction pathway.Figure 1.

Bottom Line: Here, we develop a general model of protrusion-based patterning to analyse the role of noise in this process.By analysing the effects of introducing thresholds required for signal detection in this model of lateral inhibition, our study shows how filopodia-mediated cell-cell communication can generate complex patterns of spots and stripes, which, in the presence of signalling noise, align themselves across a patterning field.Thus, intermittent protrusion-based signalling has the potential to yield robust self-organizing tissue-wide patterns without the need to invoke diffusion-mediated signalling.

View Article: PubMed Central - PubMed

Affiliation: CoMPLEX, University College London, London, UK. m.cohen@ucl.ac.uk

Show MeSH
Related in: MedlinePlus