Mechanochemical Principles of Spatial and Temporal Patterns in Cells and Tissues

International audiencePatterns are ubiquitous in living systems and underlie the dynamic organization of cells, tissues, and embryos. Mathematical frameworks have been devised to account for the self-organization of biological patterns, most famously the Turing framework. Patterns can be defined in space, for example, to form stripes; in time, such as during oscillations; or both, to form traveling waves. The formation of these patterns can have different origins: purely chemical, purely mechanical, or a combination of the two. Beyond the variety of molecular implementations of such patterns, we emphasize the unitary principles associated with them, across scales in space and time, within a general mechanochemical framework. We illustrate where such mechanisms of pattern formation arise in biological systems from cellular to tissue scales, with an emphasis on morphogenesis. Our goal is to convey a picture of pattern formation that draws attention to the principles rather than solely specific molecular mechanisms. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 38 is October 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates

Mechanical regulation of substrate adhesion and de-adhesion drives a cell contractile wave during tissue morphogenesis

During morphogenesis tissue-scale forces drive large-scale deformations, yet how these forces arise from the local interplay between cellular contractility and adhesion is poorly understood. In the posterior endoderm of Drosophila embryos, a self-organized tissue-scale wave of actomyosin contractility and cell invagination is coupled with adhesion to the surrounding vitelline membrane to drive the polarized tissue deformation. We report here that this process emerges at the subcellular level from the mechanical coupling between Myosin-II activation and sequential adhesion/de-adhesion to the vitelline membrane. At the wavefront, integrin focal complexes anchor the actin cortex to the vitelline membrane and promote activation of Myosin-II, which in turn enhances adhesion in a positive feedback loop. Subsequently, upon detachment, cortex contraction and advective flow further amplify Myosin-II levels. Prolonged contact with the vitelline membrane increases the duration of the integrin-Myosin-II feedback, integrin adhesion and thus slows down cell detachment and wave propagation of the invagination. Finally, we show that the angle of cell detachment changes as a function of the strength of adhesion and modifies the tensile forces required for detachment to maintain wave propagation. This illustrates how the tissue-scale wave arises from subcellular mechanochemical feedbacks and tissue geometry

Transcriptional induction and mechanical propagation of a morphogenetic wave

Tissue morphogenesis emerges from coordinated cell shape changes driven by actomyosin contractions. Patterns of gene expression regionalize and polarize cell behaviours by controlling actomyosin contractility. Yet how mechanical feedbacks affect tissue morphogenesis is unclear. We report two modes of control over Rho1 and MyosinII activation in the Drosophila endoderm. First, Rho1/MyoII are induced in a primordium via localized transcription of the GPCR ligand Fog. Second, a tissue-scale wave of Rho1/MyoII activation and cell invagination progresses anteriorly. The wave does not require sustained gene transcription, and is not governed by regulated Fog delivery. Instead, MyoII inhibition blocked acute Rho1 activation and propagation, revealing a mechanical feedback driven by MyoII. Last, we identify a cycle of 3D cell deformations whereby MyoII activation and invagination in each row of cells drives adhesion to the vitelline membrane, apical spreading, MyoII activation and invagination in the next row. Thus endoderm morphogenesis emerges from local transcriptional initiation and a mechanically driven wave of cell deformation

Genetic induction and mechanochemical propagation of a morphogenetic wave

International audienc

Unified quantitative characterization of epithelial tissue development.

International audienceUnderstanding 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