Organs in the human body have complex networks of fluid-filled tubes and loops. They have different shapes and their three-dimensional structures are interconnected differently depending on the organ. During the development of an embryo, organs develop their shape and tissue architecture from a simple group of cells. Due to a lack of concepts and tools, it is difficult to understand how the shape and complex tissue network arise during organ development. Scientists from the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) and the MPI for the Physics of Complex Systems (MPI-PKS), both in Dresden, have now defined metrics for organ development for the first time and the Research Institute for Molecular Pathology (IMP ) in Vienna. In their study, the international research team provides the necessary tools to turn the field of organoids – miniature organs – into an engineering discipline to develop model systems for human development.
The collective interaction of cells leads to the formation of an organism during development. The different organs exhibit different geometries and differently connected three-dimensional structures that determine the function of fluid-filled tubes and loops in organs. One example is the kidney’s branched network architecture, which supports efficient blood filtration. Observing embryonic development in a living system is difficult, which is why there are so few concepts describing how the networks of fluid-filled tubes and loops evolve. While previous studies have shown how cellular mechanics induces local shape changes during the development of an organism, how tissue connectivity arises is not clear. Combining imaging and theory, researcher Keisuke Ishihara began working on this question first in Jan Brugues’ group at MPI-CBG and MPI-PKS. He later continued his work in the group of Elly Tanaka at the IMP. Together with his colleague Arghyadip Mukherjee, formerly a researcher in Frank Jülicher’s group at the MPI-PKS, and Jan Brugués, Keisuke used organoids derived from mouse embryonic stem cells, which form a complex network of epithelia that line organs and act as a barrier. “I still remember the exciting moment when I realized that some organoids had turned into tissue with multiple buds that looked like a bunch of grapes. However, describing the change in three-dimensional architecture during development proved difficult,” recalls Keisuke, adding: “I found that this organoid system creates amazing internal structures with many loops or passages, resembling a toy ball with holes. “
Studying tissue development in organoids has several advantages: They can be observed using advanced microscopy methods, revealing dynamic changes deep in the tissue. They can be spawned in large numbers and the environment can be controlled to affect development. The researchers were able to examine the shape, number and connectivity of the epithelium. They tracked changes in the internal structure of organoids over time. Keisuke continues, “We discovered that tissue connectivity arises from two distinct processes: either two separate epithelia fuse, or a single epithelium fuses itself by fusing its two ends, thereby creating a donut-shaped loop.” based on the theory of epithelial surfaces propose that the inflexibility of epithelia is a key parameter that controls epithelial fusion and thus the development of tissue connectivity.
The supervisors of the study, Jan Brugues, Frank Jülicher and Elly Tanaka, conclude: “We hope that our results will lead to a new view of complex tissue architectures and the interplay of shape and network connectivity in organ development.” analytical frameworks will help the organoid community to characterize and design self-assembling tissues that mimic human organs. By revealing how cellular factors influence organ development, these results may also be useful for developmental cell biologists interested in organizational principles.”
Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG)
Ishara, K et al. (2022) Topological morphogenesis of neuroepithelial organoids. natural physics. doi.org/10.1038/s41567-022-01822-6.
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