Dissecting the subcellular forces sculpting earlyC. elegansembryos

Abstract

Embryo shape is governed by the mechanics of individual cells, the strength of intercellular interactions, and geometrical constraints. Models in which cells interact through surface tensions successfully predict cell arrangement within aggregates. However, predicting cell shape dynamics remains challenging because of difficulties in measuring temporal changes in tensions. Here, we dissect the spatiotemporal changes in cellular surface tensions that sculpt the early nematode embryo, using AFM measurements and inverse modeling. We validate a hybrid tension inference pipeline that combines dynamic information from cell geometry and cortical myosin enrichment. The inferred spatiotemporal tensions allow prediction of morphogenesis in wild-type embryos as well as phenotypic changes arising from protein depletion. We further uncover a direct and non-affine contribution of cadherins to cell contact tensions, whose magnitude is comparable to cadherins' indirect contribution via actomyosin regulation. Overall, our inference pipeline allows characterization of the forces underlying morphogenesis and their relationship to molecular processes.

Embryo mechanics cartography: inference of 3D force atlases from fluorescence microscopy

“…Therefore, simultaneous tension and pressure inference may not be a good strategy in this case [39], while breaking down the inference in two successive steps still allows us to infer tensions independently of cell pressures. Interestingly, we find, in agreement with the measurements in [71], a lower cell-medium tensions in P2 and EMS cells in the 4-cell stage C. elegans embryo, and predict a general trend of lower cell-medium cortical tension in descendants of the P-lineage at subsequant stages of embryo development (Fig. 6b).…”

“…We confirm this characteristic with 3D simulations of a 4 cell embryo confined within an ellipsoid (Fig. 6a), using realistic parameters that we previously measured in [71]. In this realistic simulation, we show that the mean curvature may be locally perturbed by the shell along cell-medium interfaces, especially for ABp and EMS blastomeres, which precludes the use of Laplace's law, which assumes constant mean curvature interfaces.…”

“…One forthcoming challenge will be to generate spatio-temporal mechanical atlases of various Indeed, a temporal reference is so far missing to calibrate the successive spatial maps in time. As demonstrated in 2D [71], combining static inference with the temporal measurement of absolute forces in a single location, or imaging phosphomyosin fluorescence intensity as a proxy for tension, could become a generic approach to construct temporal atlases of absolute mechanical forces, but this needs to be repeated in 3D.…”

“…Unlike the ascidian and, to a certain extent, mouse embryos, an eggshell strongly constrains the shape of cells from the zygote stage. This confinement has shown to be an essential cue controlling early cell arrangement [70,71] and makes Laplace's law no longer adequate to account for cell pressures, which are directly affected by the mechanical resistance of the shell. We confirm this characteristic with 3D simulations of a 4 cell embryo confined within an ellipsoid (Fig.…”

Germ fate determinants protect germ precursor cell division by restricting septin and anillin levels at the division plane

“…For P2 and neighboring cell surface tension analysis (Figure 3, Cell surface tension analysis was done as recently described 101 with a few modifications.…”