The large-scale movements that construct complex three-dimensional tissues during development are governed by universal physical principles. Fine-grained control of both mechanical properties and force production is crucial to the successful placement of tissues and shaping of organs. Embryos of the frog provide a dramatic example of these physical processes, as dorsal tissues increase in Young's modulus by six-fold to 80 Pascal over 8 h as germ layers and the central nervous system are formed. These physical changes coincide with emergence of complex anatomical structures, rounds of cell division, and cytoskeletal remodeling. To understand the contribution of these diverse structures, we adopt the cellular solids model to relate bulk stiffness of a solid foam to the unit size of individual cells, their microstructural organization, and their material properties. Our results indicate that large-scale tissue architecture and cell size are not likely to influence the bulk mechanical properties of early embryonic or progenitor tissues but that F-actin cortical density and composition of the F-actin cortex play major roles in regulating the physical mechanics of embryonic multicellular tissues.

Summary During early cardiogenesis, bilateral fields of mesenchymal heart progenitor cells (HPCs) move from the anterior lateral plate mesoderm to the ventral midline undergoing a mesenchymal-to-epithelial transition (MET) en route to form a single epithelial sheet. Through tracking of tissue level deformations in the heart forming region (HFR) as well as movement trajectories and traction generation of individual HPCs, we find the onset of MET correlates with a peak in mechanical stress within the HFR and changes in HPC migratory behaviors. Small molecule inhibitor treatments targeting actomyosin contractility reveal a temporally specific requirement of bulk tissue compliance to regulate heart development and MET. Targeting mutant constructs to modulate contractility and compliance in the underlying endoderm, we find MET in HPCs can be accelerated in response to microenvironmental stiffening and can be inhibited by softening. To test whether MET in HPCs was responsive to purely physical mechanical cues, we mimicked a high stress state by injecting an inert oil droplet to generate high strain in the HFR, demonstrating that exogenously applied stress was sufficient to drive MET. MET-induced defects in anatomy result in defined functional lesions in the larval heart implicating mechanical signaling and MET in the etiology of congenital heart defects. From this integrated analysis of HPC polarity and mechanics, we propose that normal heart development requires bilateral HPCs to undergo a critical behavioral and phenotypic transition on their way to the ventral midline and that this transition is driven in response to the changing mechanical properties of their endoderm substrate.