Unified quantitative characterization of epithelial tissue development
- Institut Curie, France
- Aix Marseille Université, France
- Meiji University, Japan
- Kyoto University, Japan
- Univsersité Paris-Diderot, France
Abstract
Understanding the mechanisms regulating development requires a quantitative characterization of cell processes including cell divisions, rearrangements, cell size and shape changes, and apoptoses. We developed a multiscale formalism that unifies and relates the characterizations of each individual cell process and of epithelial tissue growth and morphogenesis during development. We applied this formalism to two Drosophila proliferative tissues and by analyzing more than 9 million cell contours, we obtained comprehensive statistical maps of morphogenetic events linking cell and tissue scale dynamics. By quantifying each cell process separately in both wild-type and mutant conditions, we analyzed the roles of cell proliferation and its interplay with cell rearrangements and cell shape changes. Furthermore, by combining the formalism with mechanical stress measurement, we uncovered unexpected interplays between the patterns of tissue elongation, cell division orientation and stress orientations. Collectively, our formalism provides a novel and rigorous approach to uncover mechanisms governing tissue development.
Article and author information
Author details
Copyright
© 2015, Guirao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 6,021
- views
-
- 1,816
- downloads
-
- 189
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Unified quantitative characterization of epithelial tissue development
eLife 4:e08519.
https://doi.org/10.7554/eLife.08519
Further reading
-
- Cell Biology
- Physics of Living Systems
Cell mechanical properties determine many physiological functions, such as cell fate specification, migration, or circulation through vasculature. Identifying factors that govern the mechanical properties is therefore a subject of great interest. Here, we present a mechanomics approach for establishing links between single-cell mechanical phenotype changes and the genes involved in driving them. We combine mechanical characterization of cells across a variety of mouse and human systems with machine learning-based discriminative network analysis of associated transcriptomic profiles to infer a conserved network module of five genes with putative roles in cell mechanics regulation. We validate in silico that the identified gene markers are universal, trustworthy, and specific to the mechanical phenotype across the studied mouse and human systems, and demonstrate experimentally that a selected target, CAV1, changes the mechanical phenotype of cells accordingly when silenced or overexpressed. Our data-driven approach paves the way toward engineering cell mechanical properties on demand to explore their impact on physiological and pathological cell functions.
-
- Physics of Living Systems
Proteins containing prion-like low complexity domains (PLDs) are common drivers of the formation of biomolecular condensates and are prone to misregulation due to amino acid mutations. Here, we exploit the accuracy of our residue-resolution coarse-grained model, Mpipi, to quantify the impact of amino acid mutations on the stability of 140 PLD mutants from six proteins (hnRNPA1, TDP43, FUS, EWSR1, RBM14, and TIA1). Our simulations reveal the existence of scaling laws that quantify the range of change in the critical solution temperature of PLDs as a function of the number and type of amino acid sequence mutations. These rules are consistent with the physicochemical properties of the mutations and extend across the entire family tested, suggesting that scaling laws can be used as tools to predict changes in the stability of PLD condensates. Our work offers a quantitative lens into how the emergent behavior of PLD solutions vary in response to physicochemical changes of single PLD molecules.
