Measure organ development

The organs in the human body consist of complex networks of fluid-filled vessels and loops. They are shaped differently and their three-dimensional structures are connected differently depending on the organ. While an embryo is developing, the organs form their shape and tissue architecture from a simple group of cells. Until now, there has been a lack of concepts and tools to investigate how shape and the complex tissue network emerge during organ development. Scientists at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) and the MPI for the Physics of Complex Systems (MPI-PKS), both in Dresden, as well as the Research Institute of Molecular Pathology (IMP) in Vienna have now defined for the first time measurement criteria for organ development. This study provides the necessary tools to transform the field of organoids ¬– miniature organs – into an engineering discipline and to develop model systems for human development.

The development of an organism requires a complex interaction of cells. Different organs have different geometric shapes and differently linked three-dimensional structures that determine the function of the fluid-filled vessels and loops in the organs. One example of this is the branched network architecture of the kidney, which supports efficient blood filtration. It is difficult to observe embryonic development in a living system. Therefore, there are few concepts that describe how the networks of fluid-filled vessels and loops develop. Previous studies have shown how cell mechanics induce local shape changes during the development of an organism. However, it is not clear how the connections between the tissues come about. 

Researcher Keisuke Ishihara initially worked on this question in Jan Brugués group at the MPI-CBG and MPI-PKS, combining imaging techniques and theory. He later continued his work in Elly Tanaka's group 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 worked with organoids from mouse embryonic stem cells that form a complex network of epithelia. These are tissues that line organs and often act as a barrier. „I still remember the exciting moment when I realised that some organoids had transformed into a tissue with multiple buds. They resembled a bunch of grapes. Describing the change in three-dimensional architecture during development remained difficult," Keisuke recalls, adding: "I found that this organoid system creates amazing internal structures with many loops or openings, reminiscent of a toy ball with holes."

There are many advantages to studying tissue development in organoids: unlike whole organisms, organoids can be observed with advanced microscopy techniques, revealing dynamic changes deep inside the tissue. In addition, a large number of organoids can be produced and their environment can be controlled in order to influence the course of their development. The researchers were thus able to analyse the shape, number and cross-linking of the epithelium. They observed the changes in the internal structure of the organoids over time. 

Keisuke continues: „We discovered that the connections in the tissue are formed by two different processes: Either two separate epithelia fuse or a single epithelium fuses itself by connecting its two ends, forming a donut-shaped loop." Based on the epithelial surface theory, the researchers hypothesise that the inflexibility of the epithelia is a key parameter that controls epithelial fusion and thus the development of tissue cross-linking.

Jan Brugues, Frank Jülicher and Elly Tanaka, who led the study, conclude: „We hope that our results will lead to a new way of looking at complex tissue architectures and the interplay of shape and network connectivity in organ development. Our study will help to explore and further develop organoids. In addition, we show how cellular factors influence organ development, which is interesting for developmental cell biologists interested in organisational principles."

Source: Max Planck Institute of Molecular Cell Biology and Genetics. In: idw from 21 November 2022