One significant question in the fields of biology and biophysics is how tissues in three dimensions are formed throughout the development of animals. Teams of researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, the Excellence Cluster Physics of Life (PoL) at the TU Dresden, and the Center for Systems Biology Dresden (CSBD) have discovered how tissues can be “programmed” to transform from a flat form into a three-dimensional structure. To investigate this, the team focused on the developmental process of the fruit fly Drosophila, specifically its wing disc pouch, which changes from a shallow dome to a curved fold before becoming the adult fly’s wing.
The researchers created a technique to track three-dimensional shape changes and examine the behavior of cells during this evolution. By applying a physical model based on shape programming, they identified that the movements and reorganization of cells are crucial in determining the tissue’s shape. Their findings, published in Science Advances, suggest that shape programming may be a prevalent mechanism for understanding tissue formation in animals.
Epithelial tissues consist of closely connected cell layers and form the foundational structure of various organs. To develop fully functioning organs, these tissues must alter their shapes in three dimensions. Although some mechanisms for such three-dimensional alterations have been investigated, they fail to fully account for the variety of shapes seen in animal tissues. For instance, during the wing disc eversion in fruit flies, the wing changes from a single layer of cells to a double layer. The exact process by which the wing disc pouch shifts from a radially symmetric dome to a curved fold is still not understood.
The research teams led by Carl Modes at MPI-CBG and CSBD and Natalie Dye at PoL, who was previously with MPI-CBG, aimed to uncover how this transformation occurs. “For our explanations, we drew inspiration from ‘shape-programmable’ inanimate materials, such as thin hydrogels that can morph into three-dimensional shapes due to internal stresses when prompted,” explains Natalie Dye. She adds, “These materials can alter their internal structure in a controlled manner across the sheet to achieve specific three-dimensional configurations. This concept has previously aided our understanding of plant growth. However, animal tissues are more fluid, and their cells can change in shape, size, and position.”
The researchers set out to determine whether shape programming could provide insights into animal development by measuring tissue shape changes and cell activities during the Drosophila wing disc eversion—when the dome shape shifts to a curved fold shape. “Using a physical model, we demonstrated that collective, programmed cellular behaviors are adequate to produce the shape alterations observed in the wing disc pouch. This indicates that external forces from adjacent tissues are unnecessary, with cell rearrangements being the primary factor in the shape transformation of the pouch,” states Jana Fuhrmann, a postdoctoral fellow in Natalie Dye’s research team. To ensure that cell rearrangements were indeed the principal cause of pouch eversion, the researchers conducted tests reducing cell movement, revealing how this limitation hindered the tissue shaping process.
Abhijeet Krishna, a doctoral student in Carl Modes’ group during the study, elaborates: “The innovative models we created for shape programmability are connected to various forms of cell behaviors. These encompass both uniform and direction-dependent effects. While previous models addressed just one type of effect at a time, our models integrate both and directly correlate them with cell behaviors.”
Natalie Dye and Carl Modes conclude: “We found that the internal stresses resulting from active cell behaviors are what sculpt the Drosophila wing disc pouch during eversion. By utilizing our new method and a theoretical framework inspired by shape-programmable materials, we could analyze cell patterns on any tissue surface. These tools enhance our understanding of how animal tissues dynamically change their shape and size in three-dimensional space. Overall, our research reveals that early mechanical signals help organize cell activities, eventually resulting in modifications of tissue shape. The principles we outlined may be widely applicable to improve comprehension of various tissue-shaping processes.”
