Scientists provide measures of organ development

The organs in the human body contain complex networks of fluid-filled tubes and loops. They come in different shapes and their three-dimensional structures relate differently to each other, depending on the organ. During fetal development, organs develop their shape and histological structure from a simple group of cells. Because of a lack of concepts and tools, it is difficult to understand how shape and the complex network of tissues emerge during organ development. Measures of organ development have now been defined for the first time by scientists from the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) and MPI for Physics of Complex Systems (MPI-PKS), both in Dresden, as well as the Research Institute for Molecular Pathology (IMP). in Vienna. In their study, the international team of researchers presents the tools needed to transform the field of organelles – miniature organs – into an engineering discipline to develop model systems for human development.

The collective interaction of cells results in the formation of an organism during development. Different organs have different geometries and differently connected three-dimensional structures that define the function of the fluid-filled tubes and rings in the organs. An example is the structure of the branching network of the kidney, which supports efficient blood filtration. Observing embryonic development in a living system is difficult, and for this reason there are very few concepts describing how networks of tubes and fluid-filled annulus develop. While previous studies have shown how cell mechanics induce local shape changes during organism development, it is not clear how tissue connectivity arises. Combining imaging with theory, researcher Keisuke Ishihara first began working on this question in Jan Bruegge’s group at MPI-CBG and MPI-PKS. He later continued his work in Eli Tanaka’s group IMP. Together with his colleague Arghyadip Mukherjee, a former researcher in Frank Jülicher’s group at MPI-PKS, and Jan Brugués, Keisuke used organoids derived from mouse embryonic stem cells that form an intricate network of epithelium, which lines the organs and acts as a barrier.

I still remember the exciting moment when I found that some organelles had transformed into tissues with multiple buds resembling a bunch of grapes. Describing the change in 3D architecture during development proved challenging. I have found that this organic system generates amazing internal structures with many loops or passages, resembling a toy ball with holes in it.”

Keisuke Ishihara, researcher

The study of tissue development in organelles has several advantages: it can be observed using advanced microscopy methods, which makes it possible to see dynamic changes in the depths of the tissue. They can be created in large numbers and the environment can be controlled to influence development. The researchers were able to study the shape, number and connection of the epithelium. They tracked changes in the internal structure of memberships over time. Keisuke continues, “We discovered that the tissue connection arises from two different processes: either the fusion of two separate epitheliums or one epithelium self-fuses by fusing its two ends, thus creating a doughnut-shaped ring.” The researchers propose, based on the theory of epithelial surfaces, that epithelial inelasticity is a key factor controlling epithelial fusion and thus the development of tissue connectivity.

Study authors Jan Brugge, Frank Guelicher and Ellie Tanaka conclude: “We hope that our findings will lead to new insight into complex tissue structures and the interaction between shape and network connectivity in developing organs. Our experimental and analytical framework will help the organoid community characterize and engineer self-organizing tissues that mimic human organs By revealing how cellular factors influence organ development, these findings may also be useful to developmental cell biologists interested in regulatory principles.”

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Journal reference:

Ishihara, K.; et al. (2022) Topological morphology of neuroepithelial organelles. nature physics. doi.org/10.1038/s41567-022-01822-6.

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