Credit and copyright: Fleur Vissers 17 December 2025 Ancient collaboration between signals during embryonic development – PhD defense Jonas Mars Back to news On December 17th, Jonas Mars successfully defended his PhD thesis. He wrote his dissertation, entitled ‘Evolutionarily conserved crosstalk in developmental biology’ about his PhD research in the Korswagen group. Here, he investigated how different signaling pathways in cells are interconnected. Specifically, he studied pathways that regulate cell movement during embryonic development in the worm C. elegans. He compared the worm to mammals to determine to what extent the interaction between signaling pathways has been conserved throughout evolution. Crosstalk between signaling pathways. Left: two pathways with no crosstalk. Middle: direct crosstalk, where two signals activate a pathway together. Right: indirect crosstalk, where activation of one pathway is necessary to activate the other. Credit and copyright: Jonas Mars. During embryonic development, cells continuously communicate with each other via signals. This ensures that cells do the right things, such as forming new cells through cell division, moving to a specific location, or specializing into a specific cell type. These signals are sent, received, and processed via signaling pathways: chains of molecules, usually proteins, that interact with each other in chemical reactions. Signaling pathways are often described as simple chains, where one specific signal triggers only one specific response in the cell. But many pathways can stimulate or inhibit each other. This so-called ‘crosstalk’ creates a complex network of signaling pathways in the cell. Little is known about how exactly this crosstalk works. From worm to mouse Some signaling pathways have existed for millions of years and have thus been conserved during evolution. For example, there are proteins that exist in both mice and worms and transmit the same signal during the development of both species. If you were to go back to the last common ancestor of worms and mice, you would find these proteins there too. Apparently, they play such a crucial role during embryonic development that they have been preserved to this day. During his PhD, Jonas investigated the crosstalk between two conserved signaling pathways: the Wnt and Slit-Robo pathways. Both are involved in the movement of cells, or cell migration. He compared worms and mice to see whether not only the signaling pathways, but also the crosstalk between them, has been conserved throughout evolution. Conflicting signals Jonas first studied the interaction between different Wnt pathways. He did this in C. elegans: small worms about 1 mm long. The worms are transparent and can be easily genetically manipulated. This makes them very suitable for tracking cell migration during development. “We already knew that different Wnt pathways could have opposing effects on cell migration,” says Jonas. “What we wanted to understand was how this contradiction works at the molecular level.” Jonas discovered that the Wnt pathways had opposing effects on a single protein, which can be seen as the engine behind cell migration. “One Wnt pathway activates the engine, while the other inhibits it,” says Jonas. Intestinal crosstalk Jonas then investigated the crosstalk between the Wnt and Slit-Robo pathways, which were already known to be indirectly linked. Jonas discovered that this interaction occurs via the protein EVA1C. “Wnt first activates EVA1C, and EVA1C itself is needed to turn on the Slit-Robo signaling pathway,” Jonas explains. To determine whether this crosstalk is evolutionarily conserved, he compared C. elegans with lab-grown mini-intestines – intestinal organoids – derived from mice. “In both species, the same link between the signaling pathways was present. So this crosstalk is conserved,” says Jonas. In the mammalian intestine, the crosstalk between Wnt and Slit-Robo signals seems to ensure that stem cells stay in the right place. “This had not been found before in the mammalian intestine, and further research is now being done to understand exactly how this works,” says Jonas. Cross-pollination During his PhD, Jonas observed that crosstalk is important not only for cells, but also for researchers. “Interdisciplinary collaboration contributes to scientific discoveries. For example, research with intestinal organoids was really outside our comfort zone as a C. elegans lab, but it provided us with new insights into intestinal stem cell biology and showed that we could apply existing techniques from our lab in this new context as well,” says Jonas. “It also demonstrates the value of fundamental research: a simple discovery in worms turned out to provide new insights into mammalian development.” Other fields of research can also benefit from his results. For example, new knowledge about intestinal stem cells can be relevant to cancer biology, and understanding exactly how crosstalk between signaling pathways works is important for drug development, to prevent unintended effects. Keep exploring Jonas says he enjoyed his PhD from beginning to end. “Of course, not every day was amazing, but I have felt at the right place in a great research environment,” he says. A special moment was the first time he saw the EVA1C protein in the organoids. “I remember immediately texting my colleagues because we had put a lot of effort into this. This really kickstarted the project,” says Jonas. Another highlight was obtaining his academic teaching qualification at Utrecht University. “I learned a lot from this, it broadened my interests and opened up new career opportunities after my PhD,” he says. Jonas advises beginning PhD students not to hesitate to ask for help. “In the beginning of my PhD, it sometimes felt lonely to work on a project that was very new to everyone in my group, including myself. I have had a lot of help starting a new research line with organoids and learned a lot from that,” he says. Finally, Jonas advises to keep exploring: “Whether it’s directly related to your PhD project or not, think about what interests you. Is it a course, a summer school, a lecture, a hobby, or something else? Go for it. Don’t ‘only’ do a PhD, but make it your personal PhD.” After completing his PhD, Jonas spent two months hiking in the Balkans and trail running through the Dutch forests. He recently became a junior lecturer at the Faculty of Medical Sciences at Utrecht University. Here, he is involved in teaching cell biology courses, designing education materials, and tutoring a group of bachelor students. After his PhD defense, Jonas has a long Christmas holiday ahead of him.
