A mechanical atlas for embryogenesis at single-cell resolution – scEmbryoMech

The intricate 3D structures of multicellular organisms emerge through genetically-encoded or self-organized spatio-temporal patterns of mechanical stress. Cell-scale maps of gene expression during embryogenesis are now available, but connecting these to mechanical design principles that govern the emergence of embryonic shape is hampered by our inability to measure mechanical stresses at single-cell resolution, across embryos, over time.

In this project, we make use of a particularly tractable system, the ascidian embryo, and propose to construct a single-cell mechanical atlas, in 3D and in physical units, through gastrulation and up to the process of neurulation. We will then use this atlas to explore the regulatory logic of stress generation and its robustness to embryological and environmental perturbations.

Aim 1: We will develop two complementary modeling approaches. We will first build an inverse computational approach, grounded in a new physical theory of multicellular aggregates, to measure 3D force patterns from advanced light-sheet-based imaging data and biophysical measurements of material parameters. We will also develop a novel 3D generalized vertex model, which will be used in the subsequent 2 aims to explore the mechanical design, modularity and robustness of ascidian embryonic development.

Aim 2: We will combine this theory with biophysical measurements on live embryos to construct a dynamic atlas of mechanical forces in real units up to the neurula stages. Through the imaging of the dynamic patterns of myosin II activation and actin network organization embryos, we will decompose the inferred forces into their passive and active components.

Aim 3: We will combine experimental and computational approaches to analyze the modularity of the mechanical design and the robustness of ascidian morphogenesis to genetic or environmental fluctuations.

This project brings together 4 teams with complementary expertise in cell and developmental biology, theoretical and experimental physics, and computation, who will perform work that none can individually accomplish. It will push the frontiers of the theory of living matter and analyze the modularity and robustness of a particularly stereotyped and evolutionary conserved embryogenetic program.

The mechanical atlas and computational models will be publicly available through the MorphoNet morphodynamic browser.