Scientists Discover a New Mechanism for Epithelial Tissue Development

How three-dimensional tissue forms emerge during animal development is one of the fundamental questions in biology and biophysics that remains unanswered.

Researchers from the Center for Systems Biology Dresden (CSBD), the Excellence Cluster Physics of Life (PoL) at the Technical University of Dresden, and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, have now discovered a method by which tissues can be “programmed” to change from a flat state to a three-dimensional shape.

To achieve this, the scientists examined the wing disc pouch of the fruit fly Drosophila, which changes from a shallow dome shape to a curving fold and ultimately produces an adult fly's wing.

The scientists devised a technique to quantify alterations in the three-dimensional shape and examine the behaviour of cells throughout this procedure. Using a physical model based on shape programming, they discovered that a major factor in forming the tissue is the motions and reorganizations of the cells.

The research was published in the journal Science Advances. The shape programming technique may widely illustrate how animal tissues form.

Many organs are composed of layers of closely spaced cells called epithelial tissues. Tissues change their shape in three dimensions to form functional organs. Although certain methods pertaining to three-dimensional shapes have been investigated, they seem insufficient in explaining the diversity of tissue types found in animals.

For instance, a fruit fly's wing changes from having a single layer of cells to having two layers during a process known as wing disc eversion. It is unclear how the wing disc pouch transforms from a radially symmetric dome to a curved fold shape.

The goal of this shape modification was to be investigated by the study groups of Carl Modes, Group Leader at the MPI-CBG and the CSBD, and Natalie Dye, Group Leader at PoL and former member of the MPI-CBG.

To explain this process, we drew inspiration from “shape-programmable” inanimate material sheets, such as thin hydrogels, that can transform into three-dimensional shapes through internal stresses when stimulated. These materials can change their internal structure across the sheet in a controlled way to create specific three-dimensional shapes. This concept has already helped us understand how plants grow. Animal tissues, however, are more dynamic, with cells that change shape, size, and position.”

Natalie Dye, Group Leader, Max Planck Institute of Molecular Cell Biology and Genetics

The researchers observed tissue shape changes and cell behaviors during the Drosophila wing disc eversion, when the dome shape turns into a curved fold shape, to see whether shape programming could be a technique to explain animal development.

Using a physical model, we showed that collective, programmed cell behaviors are sufficient to create the shape changes seen in the wing disc pouch. This means that external forces from surrounding tissues are not needed, and cell rearrangements are the main driver of pouch shape change.”

Jana Fuhrmann, Postdoctoral Fellow, Max Planck Institute of Molecular Cell Biology and Genetics

The researchers tried decreasing cell movement, which in turn led to issues with tissue shaping, to verify that altered cells are the primary cause of pouch eversion.

The new models for shape programmability that we developed are connected to different types of cell behaviors. These models include both uniform and direction-dependent effects. While there were previous models for shape programmability, they only looked at one type of effect at a time. Our models combine both types of effects and link them directly to cell behaviors.”

Abhijeet Krishna, Doctoral Student, Max Planck Institute of Molecular Cell Biology and Genetics

Krishna was also a part of the Carl Modes group during the study.

Natalie Dye and Carl Modes concluded: “We discovered that internal stress brought on by active cell behaviors is what shapes the Drosophila wing disc pouch during eversion. Using our new method and a theoretical framework derived from shape-programmable materials, we were able to measure cell patterns on any tissue surface. These tools help us understand how animal tissue transforms their shape and size in three dimensions.”

They further added, “Overall, our work suggests that early mechanical signals help organize how cells behave, which later leads to changes in tissue shape. Our work illustrates principles that could be used more widely to better understand other tissue-shaping processes.”