The transformation of a tentacle into a foot

By Flatters & Co. (photograph) – Original source: Marvels of the universe. A popular work on the marvels of the heavens, the earth, plant life, animal life, the mighty deep, with an introd. by Lord Avebury and with contributions by leading specialists, etc., published in 2 vols in London 1911-1912. Page 264 [1]., Public Domain,

Differentiated cells are the building blocks of all multicellular organisms, including humans, animals, and plants. Thus, the cells that make up the skin are not the same as the cells that line the digestive tract, nor do they serve the same purpose. However, how these cells are able to maintain their unique characteristics remains uncertain.

One of the important regulators, the transcription factor Zic4, was identified by a team from the University of Geneva (UNIGE) and the Friedrich Miescher Institute for Biomedical Research (FMI) in Basel while studying the freshwater polyp known as Hydra. Researchers discovered that when Zic4 expression was suppressed, tentacle cells in a Hydra transformed into foot cells, giving the animal functioning feet on its head. The findings are published in Science Advances.

Stem cells, found in all multicellular organisms, divide and give rise to specialized cells as an organism grows and develops. To become specialized, cells undergo a process known as differentiation. Because of this, the cells that make up the skin’s surface will differ in morphology and physiology from the cells that make up the digestive tract or the nervous system. Seldom, certain differentiated cells can undergo a change in shape and function, and hence their identity, later in their lifetime. Transdifferentiation is the term for this phenomenon.

While the processes responsible for differentiation are widely understood, how a specialized cell is able to keep its identity and not undergo dedifferentiation or transdifferentiation are still a mystery. Species with the ability to repair or replace damaged parts of their bodies, or even complete regeneration, are excellent case studies. Some cells in such creatures undergo a temporary identity crisis or transformation before regenerating and taking on a new function. The freshwater hydra, a little invertebrate around 1.5 cm in length, fits this description well since it can regenerate any severed component throughout its lifetime.

This animal model has been used by scientists at the University of Geneva (UNIGE) and the Friedrich Miescher Institute for Biomedical Research (FMI) in Basel to identify the transcription factor Zic4, a protein found in the nuclei of hydra cells that regulates the expression of a series of target genes.

First author, senior research, and teaching assistant in the Department of Genetics and Evolution at the Faculty of Science and the Institute of Genetics and Genomics (iGE3) at UNIGE, Matthias Christian Vogg, explains that the work shows more specifically that Zic4 plays a vital role in the production and maintenance of the cells that make up the tentacles.

Scientists showed that epithelial cells on the tentacles’ outer layer may be converted into foot epithelial cells by lowering Zic4 expression by 50%. The hydra’s foot, also known as its basal disk, is its lowest body part. Its cells are highly specialized, producing mucus that helps it adhere to its surroundings. A few days after Zic4 was suppressed, the tentacle cells began to transdifferentiate, resulting in the development of feet instead of tentacles, the study’s supervisor, Brigitte Galliot, an emeritus professor in the Department of Genetics and Evolution in the Faculty of Science and at the iGE3 of the UNIGE, explains.

The research team also learned that transdifferentiated cells enter the cell cycle again before dividing. Because of this, they are no longer in their original identities. Charisios Tsiairis, a junior group leader at the FMI and co-last author of the paper, notes that these cells restart the process of DNA synthesis, and hence of chromosomal duplication, which is at work during cell proliferation but falls short of mitotic division.

Zic4 gene suppression was achieved by “electroporating” chemicals that silence the gene into the animal’s epidermis. Then, the researchers double labeled the cells to find a marker for tentacle cells as well as a marker for foot cells, demonstrating that these cells are transdifferentiating through a stage in which they are both tentacle and foot cells. The transdifferentiating process may be recognized by this transitional state, Chrystelle Perruchoud, a research assistant at the iGE3 of the UNIGE and in the Department of Genetics and Evolution in the Faculty of Science, says.

These findings offer new insights into the phenomenon of transdifferentiation. It’s possible that these discoveries will lead to the development of novel medicines for regenerating certain cell types in individuals that have been damaged. Many issues are still unclear at this time. In other species, does Zic4 serve the same purpose? Suppose it is possible to further suppress its expression, would it pave the way for the creation of new cell types? Furthermore, it is likely that there are additional key regulators of transdifferentiation that have not yet been identified according to the researchers.


Matthias Christian Vogg et al. (2022). The transcription factor Zic4 promotes tentacle formation and prevents epithelial transdifferentiation in Hydra, Science Advances. DOI: 10.1126/sciadv.abo0694