Small fold – big role: A tissue fold known as the cephalic furrow, an evolutionary novelty that forms between the head and the trunk of fly embryos, plays a mechanical role in stabilizing embryonic tissues during the development of the fruit fly Drosophila melanogaster.
Combining theory and experiment: Researchers integrated computer simulations with their experiments and showed that the timing and position of cephalic furrow formation are crucial for its function, preventing mechanical instabilities in the embryonic tissues.
Evolutionary response to mechanical stress: The increased mechanical instability caused by embryonic tissue movements may have contributed to the origin and evolution of the cephalic furrow genetic program. This shows that mechanical forces can shape the evolution of new developmental features.
Mechanical forces shape tissues and organs during the development of an embryo through a process called morphogenesis. These forces cause tissues to push and pull on each other, providing essential information to cells and determining the shape of organs. Despite the importance of these forces, their role in the evolution of development is still not well understood.
Animal embryos undergo tissue flows and folding processes, involving mechanical forces, that transform a single-layered blastula (a hollow sphere of cells) into a complex multi-layered structure known as the gastrula. During early gastrulation, some flies of the order Diptera form a tissue fold at the head-trunk boundary called the cephalic furrow. This fold is a specific feature of a subgroup of Diptera and is therefore an evolutionary novelty of flies.
The research groups of Pavel Tomancak and Carl Modes, both group leaders at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, looked into the function of the cephalic furrow during the development of the fruit fly Drosophila melanogaster and the potential connection with its evolution. The results of their investigation are published in the journal Nature.
A genetically patterned fold with unknown function
The researchers knew that several genes are involved in the formation of the cephalic furrow. The cephalic furrow is especially interesting because it is a prominent embryonic invagination whose formation is controlled by genes, but that has no obvious function during development. The fold does not give rise to specific structures and, later in development, it simply unfolds, leaving no trace. Bruno C. Vellutini, a postdoctoral researcher in the group of Pavel Tomancak, who led the study together with Tomancak, explains, “Our original question was to uncover the genes involved in cephalic furrow formation and the developmental role of the invagination. Later on, we broadened our investigations to other fly species and found that changes in the expression of the gene buttonhead are associated with the evolution of the cephalic furrow.”
With their experiments, the researchers show that the absence of the cephalic furrow leads to an increase in the mechanical instability of embryonic tissues and that the primary sources of mechanical stress are cell divisions and tissue movements typical of gastrulation. They demonstrate that the formation of the cephalic furrow absorbs these compressive stresses. Without a cephalic furrow, these stresses build up, and outward forces caused by cell divisions in the single-layered blastula cause mechanical instability and tissue buckling. This intriguing physical role gave the researchers the idea that the cephalic furrow may have evolved in response to the mechanical challenges of dipteran gastrulation, with mechanical instability acting as a potential selective pressure.
Physical model of folding dynamics
To determine the contribution of individual sources of mechanical stress, the experimentalists in the Tomancak group teamed up with the group of Carl Modes to create a theoretical physical model that behaves like the fly embryos. Carl Modes says, “Our model can simulate the behavior of embryonic tissues in fly embryos with very few free parameters. The model was fed with the data from the experiments. First, we wanted to see how the strength of the fold affects the function of the cephalic furrow. We assumed that a strong pull inside the fold is a good buffer to counteract mechanical forces. However, we discovered that the position and timing are what really matter. The earlier the cephalic furrow forms, the better of a buffer it is, and when it forms around the middle of the embryo, it proved to have the strongest buffering effect.” This physical model provides a theoretical basis that the cephalic furrow can absorb compressive stresses and prevent mechanical instabilities in embryonic tissues during gastrulation.
A related study reveals two cellular mechanisms to prevent stress.
Another study, also focusing on mechanisms of how flies counteract mechanical stresses, is published at the same time in the Nature journal. The team led by Steffen Lemke from the University of Hohenheim, Germany, and Yu-Chiun Wang from the RIKEN Center for Biosystems Dynamics Research in Kobe, Japan, found two different ways how flies deal with compressive stress during embryonic development. Flies either feature a cephalic furrow or, if they lack one, display widespread out-of-plane division, meaning the cells divide downwards to reduce the surface area. Both mechanisms act as mechanical sinks to prevent tissue collision and distortion. The authors of the study worked together with the MPI-CBG researchers during the course of their studies.
Evolution of a small fold
Pavel Tomancak summarizes the results, “Our findings uncover empirical evidence for how mechanical forces can influence the evolution of innovations in early development. The cephalic furrow may have evolved through the genetic changes in response to the mechanical challenges of the dipteran gastrulation. We show that mechanical forces are not just important for the development of the embryo but also for the evolution of its development.”
Related Publication:
Bipasha Dey, Verena Kaul, Girish Kale, Maily Scorcelletti, Michiko Takeda, Yu-Chiun Wang, Steffen Lemke: Divergent evolutionary strategies pre-empt tissue collision in gastrulation. Nature, September 3, 2025, doi : 10.1038/s41586-025-09447-4
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