Abstract
Tracking of cells in live-imaging microscopy videos of epithelial sheets is a powerful tool for investigating fundamental processes in embryonic development. Characterizing cell growth, proliferation, intercalation and apoptosis in epithelia helps us to understand how morphogenetic processes such as tissue invagination and extension are locally regulated and controlled. Accurate cell tracking requires correctly resolving cells entering or leaving the field of view between frames, cell neighbour exchanges, cell removals and cell divisions. However, current tracking methods for epithelial sheets are not robust to large morphogenetic deformations and require significant manual interventions. Here, we present a novel algorithm for epithelial cell tracking, exploiting the graph-theoretic concept of a ‘maximum common subgraph’ to track cells between frames of a video. Our algorithm does not require the adjustment of tissue-specific parameters, and scales in sub-quadratic time with tissue size. It does not rely on precise positional information, permitting large cell movements between frames and enabling tracking in datasets acquired at low temporal resolution due to experimental constraints such as phototoxicity. To demonstrate the method, we perform tracking on the Drosophila embryonic epidermis and compare cell–cell rearrangements to previous studies in other tissues. Our implementation is open source and generally applicable to epithelial tissues.
Highlights
Live-imaging microscopy is a powerful, and increasingly quantitative, tool for gaining insight into fundamental processes during embryonic development [1,2,3]
By representing the cell sheet as a physical network in which each pair of adjacent cells shares an edge, we show that cells can be tracked between successive frames by finding the maximum common subgraph (MCS) of the two networks: the largest network of connected cells that is contained in these two consecutive frames
Cell tracking in epithelial sheets has the potential to generate a vast amount of quantitative data to inform our understanding of the contributions of different cellular processes to tissue morphogenesis
Summary
Live-imaging microscopy is a powerful, and increasingly quantitative, tool for gaining insight into fundamental processes during embryonic development [1,2,3]. Quantitative information on cell growth, proliferation, death, shape changes and movement extracted from live-imaging reveals how such processes are regulated to give correct tissue-level behaviour. This approach has been successful in characterizing the growth and patterning of embryonic epithelial tissues in a number of model organisms [4,5,6,7,8,9]. A common experimental technique for visualizing cell shapes in an epithelial sheet is to fluorescently tag a molecule marking cell boundaries, such as E-cadherin (figure 1a).
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