eLife digest | Egr-5 is a post-mitotic regulator of planarian epidermal differentiation

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Egr-5 is a post-mitotic regulator of planarian epidermal differentiation

eLife digest

Affiliation details

Stowers Institute for Medical Research, United States; Howard Hughes Medical Institute, Stowers Institute for Medical Research, United States

Tissues in adult animals contain cells called adult stem cells, which can divide to generate more adult stem cells (in a process called self-renewal) or specialize into other cell types (via a process called differentiation). This means that adult stem cells can replace the specialized cells that are continually lost from animal tissues and organs. This allows the organs to continue to work properly. It is important to understand how adult stem cells decide whether to self-renew or differentiate because if they proliferate too much they may form abnormal growths such as tumors. On the other hand, if adult stem cells do not properly differentiate into specialized cells it can lead to tissue degeneration or even premature aging.

Now Tu et al. have used planarian flatworms, which are considered masters of regeneration, as a model to study how adult stem cells differentiate into more specialized cells. In particular, the experiments explored how the flatworm’s adult stem cells (which are called neoblasts) develop into the epidermal cells that form the equivalent of the worm’s skin.

Tu et al. show that when a neoblast becomes a mature epidermal cell, it has to undergo multiple transition steps. Slightly different genes are expressed during each step, but a gene called egr-5 controls the expression of all of these marker genes. The egr-5 gene is highly expressed when cells start to develop into epidermal cells. Reducing this gene’s activity blocks the cells from differentiating properly, meaning that they do not form mature epidermal cells. The loss of new epidermal cells causes a disruption in the overall integrity of the worm’s outer surface and this triggers a wound response throughout the whole animal. The neoblasts in turn respond by proliferating excessively and generating other differentiated cells such as neurons and gut cells. However, without egr-5, the flatworms still cannot make new epidermal cells and they ultimately die.

The findings highlight that the development of epithelial cells in this relatively simple organism is much more complicated than suspected. In the future, it will be important to understand how the egr-5 gene controls the proper differentiation and maturation of epidermal cells and whether these mechanisms are conserved in other animals.

DOI: http://dx.doi.org/10.7554/eLife.10501.002