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Epithelial organisation revealed by a network of cellular contacts.

Escudero LM, Costa Lda F, Kicheva A, Briscoe J, Freeman M, Babu MM - Nat Commun (2011)

Bottom Line: Here we apply network theory at the scale of individual cells to uncover patterns in cell-to-cell contacts that govern epithelial organisation.We provide an objective characterisation of epithelia using network representation, where cells are nodes and cell contacts are links.The approach permits characterization, quantification and classification of normal and perturbed epithelia, and establishes a framework for understanding molecular mechanisms that underpin the architecture of complex tissues.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. lmescudero-ibis@us.es

ABSTRACT
The emergence of differences in the arrangement of cells is the first step towards the establishment of many organs. Understanding this process is limited by the lack of systematic characterization of epithelial organisation. Here we apply network theory at the scale of individual cells to uncover patterns in cell-to-cell contacts that govern epithelial organisation. We provide an objective characterisation of epithelia using network representation, where cells are nodes and cell contacts are links. The features of individual cells, together with attributes of the cellular network, produce a defining signature that distinguishes epithelia from different organs, species, developmental stages and genetic conditions. The approach permits characterization, quantification and classification of normal and perturbed epithelia, and establishes a framework for understanding molecular mechanisms that underpin the architecture of complex tissues.

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PCA graphs of the wildtype and mutant epithelia(a) dWP-dMWP. (b) dWP-dNP-dMWP. (c) dWP-dMWP-cEE. (d) dWP-dMWP-cEE-cNT. dWP: Wing prepupa, cNT: chicken Neural Tube, cEE: chicken Embryonic Ectoderm, dMWP: mutant Wing prepupa.
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Figure 3: PCA graphs of the wildtype and mutant epithelia(a) dWP-dMWP. (b) dWP-dNP-dMWP. (c) dWP-dMWP-cEE. (d) dWP-dMWP-cEE-cNT. dWP: Wing prepupa, cNT: chicken Neural Tube, cEE: chicken Embryonic Ectoderm, dMWP: mutant Wing prepupa.

Mentions: What regulates this reproducible long-range organization of epithelia? Several factors have been implicated in controlling the behaviour of individual cells and consequently epithelial architecture6, 8, 9, 11, 15-18. However, how global epithelial structure is determined by, for example the effect of the cytoskeleton of the cells within the epithelium is not understood. Therefore, we applied GNEO to quantify objectively the effect in the wing disc of removing myosin II heavy chain using RNAi28, 29, a genetic manipulation that robustly and uniformly disrupts the cytoskeletal organization and epithelial architecture (Methods). Both PCA and DA were clearly able to separate wildtype (WT) discs from those in which myosin II had been reduced (Fig. 3a and Supplementary Fig. S9a). Interestingly, while all WT wings formed one distinct tight cluster, the mutant wings were more broadly spread over the graph (Fig. 2a; PCA; p=4.27×10−10). This is consistent with a visual inspection of the data, which showed that reducing the levels of myosin II by RNAi knockdown disrupted epithelial organisation to different extents in different wing discs. In order to provide an objective score for the severity of the mutant phenotype, we calculated the Euclidean distance between each mutant wing and the center of mass of the WT wings (Supplementary Table S3). The coefficient of variation of the distances was ~26%, which most likely reflects the variability of the RNAi efficiency among the individuals. Individual mutant samples were between 15 and 35 times further from the center of mass than the average of the distances of the dWP samples (Supplementary Table S3).


Epithelial organisation revealed by a network of cellular contacts.

Escudero LM, Costa Lda F, Kicheva A, Briscoe J, Freeman M, Babu MM - Nat Commun (2011)

PCA graphs of the wildtype and mutant epithelia(a) dWP-dMWP. (b) dWP-dNP-dMWP. (c) dWP-dMWP-cEE. (d) dWP-dMWP-cEE-cNT. dWP: Wing prepupa, cNT: chicken Neural Tube, cEE: chicken Embryonic Ectoderm, dMWP: mutant Wing prepupa.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672852&req=5

Figure 3: PCA graphs of the wildtype and mutant epithelia(a) dWP-dMWP. (b) dWP-dNP-dMWP. (c) dWP-dMWP-cEE. (d) dWP-dMWP-cEE-cNT. dWP: Wing prepupa, cNT: chicken Neural Tube, cEE: chicken Embryonic Ectoderm, dMWP: mutant Wing prepupa.
Mentions: What regulates this reproducible long-range organization of epithelia? Several factors have been implicated in controlling the behaviour of individual cells and consequently epithelial architecture6, 8, 9, 11, 15-18. However, how global epithelial structure is determined by, for example the effect of the cytoskeleton of the cells within the epithelium is not understood. Therefore, we applied GNEO to quantify objectively the effect in the wing disc of removing myosin II heavy chain using RNAi28, 29, a genetic manipulation that robustly and uniformly disrupts the cytoskeletal organization and epithelial architecture (Methods). Both PCA and DA were clearly able to separate wildtype (WT) discs from those in which myosin II had been reduced (Fig. 3a and Supplementary Fig. S9a). Interestingly, while all WT wings formed one distinct tight cluster, the mutant wings were more broadly spread over the graph (Fig. 2a; PCA; p=4.27×10−10). This is consistent with a visual inspection of the data, which showed that reducing the levels of myosin II by RNAi knockdown disrupted epithelial organisation to different extents in different wing discs. In order to provide an objective score for the severity of the mutant phenotype, we calculated the Euclidean distance between each mutant wing and the center of mass of the WT wings (Supplementary Table S3). The coefficient of variation of the distances was ~26%, which most likely reflects the variability of the RNAi efficiency among the individuals. Individual mutant samples were between 15 and 35 times further from the center of mass than the average of the distances of the dWP samples (Supplementary Table S3).

Bottom Line: Here we apply network theory at the scale of individual cells to uncover patterns in cell-to-cell contacts that govern epithelial organisation.We provide an objective characterisation of epithelia using network representation, where cells are nodes and cell contacts are links.The approach permits characterization, quantification and classification of normal and perturbed epithelia, and establishes a framework for understanding molecular mechanisms that underpin the architecture of complex tissues.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. lmescudero-ibis@us.es

ABSTRACT
The emergence of differences in the arrangement of cells is the first step towards the establishment of many organs. Understanding this process is limited by the lack of systematic characterization of epithelial organisation. Here we apply network theory at the scale of individual cells to uncover patterns in cell-to-cell contacts that govern epithelial organisation. We provide an objective characterisation of epithelia using network representation, where cells are nodes and cell contacts are links. The features of individual cells, together with attributes of the cellular network, produce a defining signature that distinguishes epithelia from different organs, species, developmental stages and genetic conditions. The approach permits characterization, quantification and classification of normal and perturbed epithelia, and establishes a framework for understanding molecular mechanisms that underpin the architecture of complex tissues.

Show MeSH
Related in: MedlinePlus