How cells choose between two fates

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In animals with reduced levels of a protein called Zic4, tentacle cells change t
In animals with reduced levels of a protein called Zic4, tentacle cells change their identity to became foot cells (green). Image credits: Jaroslav Ferenc

Our body is made of billions of cells that have the same overall genome but play specialized roles to create different tissues and organs. Working in a freshwater invertebrate, FMI researchers found that a protein called Zic4 drives the formation and maintenance of the tentacles that surround the animal’s mouth. Dampening the levels of Zic4 makes tentacle cells change into different types of cells. The findings could help researchers to pinpoint the factors that govern the choice between two cell fates in other animals.

As an embryo develops, its stem cells differentiate into the precursors of various cell lineages that give rise to neurons, blood cells, skin cells and other types of specialized cells. However, how cell types keep their specific identity remain mysterious.

Researchers in the Tsiairis lab set out to address this question by studying the development of Hydra — a tube-like organism with a tentacle-rimmed mouth and a sticky foot, which can regrow its whole body from a small piece of tissue in a few days. The researchers identified Zic4, a transcription factor — or a protein that controls the expression of genes — as the key driver of the formation and maintenance of Hydra’s tentacles. When the levels of Zic4 were reduced, tentacle cells changed their identity and became foot cells, the team found.

The findings shed light onto the gene regulatory networks that govern the choice between two epithelial cell fates in Hydra and possibly in other animals, the researchers say.

Matthias Christian Vogg, Jaroslav Ferenc, Wanda Christa Buzgariu, Chrystelle Perruchoud, Paul Gerald Layague Sanchez, Leonardo Beccari, Clara Nuninger, Youn Le Cras, Céline Delucinge-Vivier, Panagiotis Papasaikas, Stéphane Vincent, Brigitte Galliot*, Charisios D. Tsiairis* The transcription factor Zic4 promotes tentacle formation and prevents epithelial transdifferentiation in Hydra Science Advances (2022) Advance online publication
* co-corresponding authors