How to turn a tentacle into a foot

Hydra with reduced Zic4 content. The red arrowheads indicate the tentacles that have been transformed into feet, the asterisk indicates the animal's mouth.
Illustration Credit:  Galliot, Brigitte CC-BY-NC

By identifying a key cell identity regulator, a team from UNIGE and the IMF has managed to modify the structure and function of tentacle cells in the hydra.

Humans, animals, plants: all multicellular organisms consist of so-called differentiated specialized cells. Thus, the cells that make up the epidermis do not have the same identity - nor the same function - as those that line the digestive system, for example. However, the mechanisms allowing these cells to maintain their identity are still poorly understood. Working on hydra, a team from the University of Geneva (UNIGE), in collaboration with the Friedrich Miescher Institute for Biomedical Research (IMF) in Basel, discovered one of the key regulators: the factor of transcription Zic4. After reducing its expression, researchers have found that the tentacle cells of the hydra change their identity and turn into foot cells, forming functional feet in the animal's head. These results are to be discovered in the journal Science Advances.

By identifying a key regulator of cell identity, a team from UNIGE and the IMF has succeeded in modifying the structure and function of tentacle cells in the hydra, transforming them into foot cells. This phenomenon is called transdifferentiation. 
Illustration Credit: University of Geneva, Courtesy of Dr Vogg

When a living organism develops, its stem cells divide and gradually give rise to new cells capable of performing one or more particular functions. This cell specialization process is called differentiation. Thus, the cells that make up the surface of the skin will be different, morphologically and physiologically, from those that make up, for example, the digestive tissue or the nervous system. In very rare cases, some already differentiated cells can still change structure and function - and therefore identity - during their existence. We then speak of transdifferentiation.

If the mechanisms of differentiation are known, those which allow the specialized cell to maintain its identity - and therefore to prevent its differentiation (loss of identity) or its transdifferentiation (change of identity) - remain mysterious. To study them, the species that regenerate their organs, their limbs or their entire body constitute privileged models. Within these organisms, certain cells temporarily lose their identity before renewing themselves and performing a new function. This is particularly the case with freshwater hydra, a small invertebrate measuring on average 1.5 cm, capable of regenerating any amputated part throughout its life.

A key regulator identified

Based on this animal model, researchers from the University of Geneva (UNIGE) in collaboration with the Friedrich Miescher Institute for Biomedical Research (IMF) in Basel, have identified a key regulator for maintaining cell identity: the transcription factor Zic4, either a protein located in the nuclei of the hydra cells, responsible for regulating the expression of a series of target genes. “We demonstrate more precisely that Zic4 plays a crucial role in the formation and maintenance of the cells that make up the tentacles, and by reducing its expression, it is possible to modify the organization and function of these cells ", explains Matthias Christian Vogg, assistant professor in the Department of Genetics and Evolution of the Faculty of Science and at the Institute of Genomics and Genomics (iGE3) of UNIGE, as well as the first author of the study.

By halving Zic4's level of expression, scientists have discovered that the epithelial cells of the outer layer of tentacles are transformed into epithelial cells of the foot. "The basal disk of the hydra is called foot. The cells that compose it are very specialized: they secrete mucus which allows the animal to settle in the surrounding environment. After reduction of Zic4, it only took a few days for the process of transdifferentiation of tentacle cells to take place and lead to the development of feet in place of tentacles. ", says Brigitte Galliot, honorary professor in the Department of Genetics and Evolution of the Faculty of Science and in the IGE3 of UNIGE, who supervised the study.

Published in journal: Science Advances

Source/Credit: University of Geneva

Reference Number: bio010523_01

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