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Finding the shape-shifter genes

Nature Cell Biology volume 15, pages 723–725 (2013)Cite this article

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Cell morphological plasticity is controlled by intracellular signalling pathways. By combining large-scale imaging with quantitative analysis, an RNA interference (RNAi) screen in Drosophila melanogaster haemocytes reveals that most targeted genes regulate transitions between discrete shapes. Loss of gene function changes shape frequencies or reduces diversity, rather than producing new morphologies.

Cultured cells are able to adopt a variety of shapes. However, whether an experimental treatment has induced a morphological response can be difficult to determine by visual inspection alone. The diversity of cell shapes observable in a population, combined with the generally subjective nature of morphological studies, and in some cases experimental or confirmation bias, could lead to the inadvertent selection of exemplars that 'typify' a given morphology without necessarily being truly representative. Thus, although detecting and describing morphological responses have been at the heart of cell biology research for many years, fundamental issues about how cells change shape have been challenging to address. Moreover, the approaches employed until now generally have not incorporated the large-scale, unbiased and multivariate methodologies of systems biology1. In this issue, Yin et al.2 combined RNAi screening with rigorously applied high content imaging3 and quantitative and statistical analysis to address how cell shape is regulated with respect to three related issues. Firstly, whether cells adopt a continuum of variable shapes, or whether the universe of cell shapes is comprised of discrete definable forms. Secondly, if the latter case were true, whether these discrete shapes are regulated by biological factors, and how perturbing these factors might affect cell shape choices. For example, would inhibiting the expression of a specific gene change the number of cell shapes by inducing the disappearance of existing ones and/or appearance of new ones, or would it merely change the frequency distribution between shapes? Finally, whether cell shape transitions occur as 'on–off' shape switches, or cells spend significant periods as intermediate forms.

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Figure 1: Analysis of morphological parameters demonstrates that cell shapes are discrete and definable.

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  1. Michael F. Olson is at the Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK,

    Michael F. Olson

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  1. Michael F. Olson
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Correspondence to Michael F. Olson.

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Olson, M. Finding the shape-shifter genes. Nat Cell Biol 15, 723–725 (2013). https://doi.org/10.1038/ncb2792

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