A team of researchers led by L. Mahadevan, Lola England de Valpine Professor of Applied Mathematics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), and Professor of Organismic and Evolutionary Biology, and of Physics in the Faculty of Arts and Sciences (FAS), developed a theoretical framework tha can reproduce and predict the patterns associated with gastrulation in a chicken embryo.
Gastrulation is one of the most important phases in early embryonic development. It is a operation of self-organization that requires coordinated movements of hundreds to tens of thousands of cells. Vertebrate embryos begin as simple two-dimensional sheets of cells, by the end of gastrulation, an embryo will have begun to differentiate distinct cell types, set up the basic axes of the body and internalize some of the precursors for organs in a three-dimensional structure. Amniotes, like chickens and humans, will have developed a primitive streak, the precursor to the brain and skin, while fish and amphibians will have developed a spherical-shaped blastopore. Despite gastrulation's importance in development, scientists only partially understand the underlying mechanisms that coordinate this large-scale movement of cells.
The team of researchers from the Harvard, the University of California San Diego and the University of Dundee in the U.K., developed a theoretical and and computational model that could recreate the movement of the epithelial layer of cells in chick embryos during gastrulation. They then identified two parameters — one related to the initial distribution of cells in an embryo and the other related to cell behavior — to tweak during gastrulation. By changing these two parameters in chicken development, they saw new patterns seen naturally in other species.
“Our work suggests that the general biophysical principles underlying active self-organized flows and forces during embryogenesis have the power to explain developmental processes and their evolutionary variations across different species of vertebrates,” said Mahadevan.
The study, published in Science Advances, illuminates the principles for self- organization in early development, and may also help researchers understand the evolutionary history of developmental processes and suggest ways to control the development of synthetic organoids.
Image: Changing cell behaviors and initial cell types, (left column), the model recapitulates the flow patterns in the phylogeny of vertebrate gastrulation from a self-organizing dynamical structure. The model-based predicted flow patterns mimic those naturally observed in reptiles, amphibians, and fish, and are reproduced experimentally, in vivo, in the chick embryo. The right columns show deformed Lagrangian grids overlaying the light-sheet microscope images from perturbed chick-experiment velocities and deformed Lagrangian grids from the predicted model velocity for each gastrulation mode. (Credit: Harvard SEAS)