Copyright Hubrecht Institute, credit: Jelmer Hoeksma 24 June 2025 Zebrafish grow a second tail: unexpected insights into tail development Back to news Researchers from the group of Jeroen den Hertog have uncovered a surprising mechanism behind tail formation in zebrafish embryos. In a study published in Development, they show that a group of cells derived from a transient organ called Kupffer’s vesicle plays an essential role in normal tail development. When these cells fail to migrate properly, an extra tail can form. This reveals a previously unknown population of tail progenitors. Copyright: Hubrecht Institute, credit: Jelmer Hoeksma. From fungal molecules to embryonic tails The discovery stems from an ongoing project at the Hubrecht Institute aimed at identifying bioactive compounds from fungi using zebrafish embryos as a model system. During this screen, researchers encountered a particularly striking effect: embryos exposed to a filtrate from the fungus Ceratocystis populicola developed a second tail. Chemical analyses traced the effect to a class of molecules called monoterpenes, volatile compounds also found in some perfumes and deodorants. The monoterpene geraniol turned out to be especially potent. Embryos treated with geraniol during a specific four-hour window of early development consistently developed second tail-like structures, alongside defects in the notochord and overall body length. Cells from the Kupffer's vesicle (green) fail to migrate when the zebrafish were treated with geraniol (bottom), while they spread throughout the tail in fish that were not treated with geraniol (top). Copyright: Hubrecht Institute, credit: Jelmer Hoeksma. Cells from a dissolving organ fail to migrate Normally, once Kupffer’s vesicle has fulfilled its role, it collapses and its epithelial cells migrate towards the forming tail, where they contribute to normal tissue development. These cells help form key structural components of the tail, including the presomitic mesoderm (the precursor of muscle segments), the somites (blocks of mesoderm that give rise to vertebrae and muscles), and the notochord (a central supporting structure). In embryos treated with geraniol, however, these cells fail to migrate and instead remain at their original location. There, they cluster together and begin forming a second tail-like structure, expressing genes typical of tail tissues, but notably lacking markers of neural tissue. This absence suggests that, although the structure resembles a tail, it does not include the spinal cord, highlighting the specific developmental potential, and limitations, of these cells. A surprising role for Kupffer’s vesicle cells To test whether these vesicle-derived cells are truly responsible for the second tail, the researchers blocked the formation of Kupffer’s vesicle using a genetic technique. In these embryos, geraniol treatment no longer led to second tail formation, while the normal tail still developed. This shows that the second tail specifically arises from Kupffer’s vesicle-derived cells, and that in normal development, these cells likely integrate into the primary tail. When this process is disrupted, for instance by geraniol, they remain behind and initiate a second tail-like structure. The experiment highlights how tightly controlled cell migration is essential to ensure that only one tail forms. A curious path to discovery This study highlights how exploratory, curiosity-driven research can lead to unexpected biological insights. What began as a screen for fungal metabolites ended in a fundamental discovery about vertebrate development. The identification of a new population of tail progenitors and the mechanism behind ectopic tail formation opens new avenues for studying how tissues self-organize during development, and how things can go awry. Videos Kupffer's vesicle cells fail to migrate in geraniol treated embryos × Publication Migration of Kupffer’s vesicle-derived cells is essential for tail morphogenesis in zebrafish embryos. Jelmer Hoeksma and Jeroen den Hertog. Development, 2025. Jeroen den Hertog is group leader and managing director at the Hubrecht Institute and professor of Molecular Developmental Zoology at Leiden University
