Interplay of mechanical and biochemical cues in self-organization processes during embryogenesis - Part II

• Applicant: Professor Dr. Matthias Weiss
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Biophysics
• Term: from 2014 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257444317

Dynamic self-organization phenomena in multi-cellular organisms not only relies on genetic and molecular-biological factors but it is also based to a considerable extent on physical cues, e.g. on the integration of intercellular mechanical forces. Despite significant progress in recent years, the interplay of these different signals is still poorly understood. A prominent example in this context is the early embryogenesis of the roundworm Caenorhabditis elegans that proceeds in an almost invariant fashion in all individuals, resulting in the very same number of cells in all adults. This remarkable and almost deterministic reproducibility invokes biochemical signaling cascades as well as mechanical forces, hence making C. elegans a distinguished model organism for studying the interplay of these two cues. During the first period, we were able to significantly advance our previous preliminary work: Using dual-color selective plane illumination microscopy (SPIM) we have revealed the quantitative relation between cell volumes and division times, hence fixing an important aspect of the interplay between mechanical and biochemical signals. This experimental result was also successfully integrated into a simple simulation model for dynamic cell arrangements. In addition, we also have achieved a quantitative physical understanding of important asymmetric cell divisions up to gastrulation. Moreover, we have determined heterogeneous diffusion maps of proteins in individual cells of the embryo via SPIM-FCS. Based on these, meanwhile mostly published results we intend to address further central aspects of the coupling of mechanical and biochemical cues in the early embryogenesis of C. elegans in a final funding period. Experiments will focus here on (1) the influence of altered mechanical constraints (e.g. embryos without confining eggshell), (2) the partially active cell migration during gastrulation, and (3) the interplay of actomyosin-based force fields and intracellular protein and mobility gradients as potential determinants of cell division axes. To this end, the orientation of mitotic spindles, flow fields of actomyosin networks, and the localization of polarity proteins in embryos of different transgenic worm strains will be quantified in a spatiotemporally resolved fashion via SPIM, SPIM-FCS, and spinning-disk confocal microscopy. In these experiments we will also exploit altered mechanical constraints and/or RNAi-mediated knockdown of certain signaling cascades. Data from these extensive experiments and their mutual correlations will fuel the refinement of the simulation model for mechanically triggered self-organization of cells during the embryogenesis of C. elegans. Within the requested final funding period we aim at a quantitative and predictive description of embryonic cell arrangement deep into the gastrulation phase.

• DFG Programme: Research Grants