Unified quantitative characterization of epithelial tissue development

Abstract

Understanding the mechanisms regulating development requires a quantitative characterization of cell divisions, rearrangements, cell size and shape changes, and apoptoses. We developed a multiscale formalism that relates the characterizations of each cell process to tissue growth and morphogenesis. Having validated the formalism on computer simulations, we quantified separately all morphogenetic events in the Drosophila dorsal thorax and wing pupal epithelia to obtain comprehensive statistical maps linking cell and tissue scale dynamics. While globally cell shape changes, rearrangements and divisions all significantly participate in tissue morphogenesis, locally, their relative participations display major variations in space and time. By blocking division we analyzed the impact of division on rearrangements, cell shape changes and tissue morphogenesis. Finally, by combining the formalism with mechanical stress measurement, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our formalism provides a novel and rigorous approach to uncover mechanisms governing tissue development.DOI: http://dx.doi.org/10.7554/eLife.08519.001

SEGGA: a toolset for rapid automated analysis of epithelial cell polarity and dynamics

“…Fully automated methods for image segmentation and analysis, which are optimized for speed, increase the throughput of data analysis by tolerating a non-negligible frequency of errors that would otherwise require substantial effort to correct. These methods are well suited for large tissues in which error correction is impractical, short-term behaviors during which time errors are less likely to accumulate, and tissues that do not undergo substantial rearrangement Aigouy et al, 2010;Fernandez et al, 2010;Bosveld et al, 2012;Mosaliganti et al, 2012;Khan et al, 2014;Guirao et al, 2015;Heller et al, 2016;Stegmaier et al, 2016). However, segmentation errors that lead to 1% untracked cells in each frame of a movie are predicted to interrupt more than half of all cell trajectories after 70 time points, making fully automated methods of limited use for long-term tracking.…”

Emergence of epithelial cell density waves

“…of epithelial cell monolayers is known to fluctuate in both time and space, both in vitro [24,25] and in vivo [26]: the corresponding epithelial flows are thus compressible.…”

Using cell deformation and motion to predict forces and collective behavior in morphogenesis

“…Recent techniques allow imaging of developing organs or even entire embryos in vivo , as well as automated tracking of the motion and deformation of each individual cell [11–17]. From such data, tissue deformation can be quantified in a straightforward manner using particle image velocimetry [13, 18].…”

“…To precisely quantify the contribution of each cellular event to the overall deformation based on segmented image data, two classes of methods have been developed [11, 15, 17, 25–31]. The first class focuses on the shape of cell outlines and their deformation [11, 12, 25, 27, 28].…”