Nature sub-journal: Measuring organ development

Human organs have a complex network
of fluid-filled pipes and circuits.
They come in different shapes, and their three-dimensional structures connect to each other differently, depending on the organ
.
During the development of the embryo, organs develop their shape and organizational structure
from a simple set of cells.
Understanding how complex tissue networks are formed during organ development is challenging due to a lack of concepts and tools
.
Now, 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) in Dresden, as well as the Vienna Institute for Molecular Pathology (IMP), have defined for the first time indicators
of organ development.
In their research, the international research team provided the necessary tools to translate the field of organoids (miniature organs) into an engineering discipline to develop model systems
for human development.

During development, the collective interaction of cells leads to the formation
of organisms.
Different organs have different geometries and three-dimensional structures with different connections that determine the function
of the fluid-filled tubes and rings in the organ.
One example is the branch network structure of the kidney, which supports efficient filtration
of blood.
Observing embryonic development in a living system is difficult, which is why there are few concepts describing how fluid-filled pipes and circulatory networks develop
.
While past studies have shown how cellular mechanics induces changes in local shape during the development of an organism, it is unclear how tissue connectivity emerges
.
By combining imaging and theory, researcher Keisuke Ishihara first began working on this question
in Jan Brugues' team at MPI-CBG and MPI-PKS.
He later continued his work
in the Elly Tanaka group at IMP.
Keisuke, along with his colleague Arghyadip Mukherjee, used organoids from mouse embryonic stem cells to form a complex network of epithelial cells that connect organs and act as
barriers.
"I remember that exciting moment when I discovered that some organoids had been transformed into tissue with multiple buds, which looked like a bunch of grapes
.
However, describing changes in three-dimensional structure during development proved challenging," Keisuke recalls, adding, "I found that this organ system produced amazing internal structures with many loops or channels, like a toy ball
with holes.
" ”

Studying the development of organoid tissues has several advantages: they can be observed with advanced microscopic methods, making it possible to see dynamic changes
deep inside the tissue.
They can be produced in large quantities and the environment can be controlled to influence development
.
Researchers were able to study the shape, number, and connectivity of epithelial cells
.
They tracked changes in the organoid's internal structure over time
.
Keisuke continues, "We found that tissue connectivity comes from two different processes: either two separate epithelial cells fuse, or a single epithelial cell fuses itself by fusing its two ends, creating a doughnut-shaped ring
.
" The researchers proposed that, based on epithelial surface theory, epithelial inflexibility is a key parameter to control epithelial fusion, thereby developing tissue connectivity
.

Jan Brugues, Frank Jülicher and Elly Tanaka, leaders of the study, concluded: "We hope that our findings will lead to new insights
into the interactions between shape and network connections in complex tissue structures and organ development.
Our experimental and analytical framework will help organoid populations describe and design self-organizing tissues
that mimic human organs.
By revealing how cellular factors affect organ development, these results may also be useful
to developmental cell biologists interested in tissue principles.
”

Journal Reference:

1. Ishihara, K.
   , Mukherjee, A.
   , Gromberg, E.
   et al.
   Topological morphogenesis of neuroepithelial organoids.
   Nat.
   Phys.
   , 2022 DOI: 10.
   1038/s41567-022-01822-6