A research team led by Dr. Y. Lin from the Department of Mechanical Engineering at the University of Hong Kong have made major breakthrough in elucidating how force-induced cellular anisotropy and plasticity dictate the elongation dynamics of embryos, a fundamental question not well understood by scientists before. The findings have recently been published in Science Advances (https://doi.org/10.1126/sciadv.abg3264).
During its development, the embryo can undergo a several-fold elongation, driven by contractile forces generated in muscle and seam cells in the embryonic wall, without losing its structural integrity. Recent studies have demonstrated that this extension process is accompanied with the appearance of significant cytoskeletal anisotropy and plastic deformation of cells. However, how such cellular anisotropy and plasticity are developed as well as their role in embryo development remain unclear.
Dr. Lin and his team presented a theoretical study to show that the presence of active intracellular/intercellular contraction will trigger the alignment and severing/re-bundling of actin filaments (Fig. 1), leading to cellular anisotropy and plasticity, elevate the internal hydrostatic pressure of embryo and eventually drive its elongation. In particular, it was found that the gradual re-alignment of F-actins must be synchronized with the development of intracellular forces for the embryo to elongate, which is then further sustained by muscle contraction-triggered plastic deformation of cells. Furthermore, the model predicts that pre-established anisotropy is essential for the proper onset of the process while defects in the integrity or bundling kinetics of actin bundles result in abnormal embryo elongation, all in good agreement with experimental observations (Fig. 2).
In addition to serve as a major step in furthering our fundamental understanding of embryo mechanics, this study also represents a novel direction in investigating processes such as tissue morphogenesis and collective cell migration where the development of active cellular stresses and significant cytoskeleton remodeling/damage have all been believed to play key roles.
Figure 1. Schematic diagrams of C. elegans embryo elongation. (A) Cartoons showing two stages of elongation driven by seam cell and muscle contractions. (B) Illustration of the microstructure of the embryo wall (treated as a thin-walled cylinder). Contraction generated in seam cells causes the shrinking of the embryo wall in the circumferential direction and eventually drives its axial elongation. Such elongation is further sustained by contraction of body-wall muscles in the second stage. (C) Illustration of the model where the development of cellular anisotropy and plasticity were assumed to be caused by the force-induced alignment and severing/re-bundling of actin filaments, respectively.
Figure 2. Comparisons between model predictions and experiments. (A) Model outputs agree well with measured elongation trajectories of wild type and different mutant embryos. (B) The predicted evolution of normalized embryo diameter beyond 1.3-fold elongation also compares favourably with experimental observations.