When Deprived of Nerve Cells, Hydra Rears Compensatory Gene Program

Though tiny, the freshwater Hydra has regenerative abilities more impressive than those of its namesake, the nine-headed monster of Greek legend. Both the real Hydra and the mythical Hydra can undergo morphallaxis—tissue regeneration—when body parts are injured or severed. But the real Hydra has an extra trick up its sleeve, or down its collar. The real Hydra can survive the loss of its nervous system.

The Hydra is able to regulate behaviors such as contraction bursts, touch response, light response, feeding, walking, and swimming thanks to a fairly sophisticated nervous system, which incorporates various kinds of nervous cells, all of which arise from multipotent stem cells named interstitial stem cells (i-cells). Yet when the Hydra deprived of i-cells, it maintains its developmental fitness, regenerates, and buds, even though it loses its active behaviors.

The Hydra manages this feat through a kind of cellular plasticity. It activates a genetic program that alters epithelial cells so that they can assume at least a few neurological duties. Epithelial cells do not ordinarily carry out neuronal functions. But in the epithelial cells of Hydra, a series of genes that are involved some of these functions can be overexpressed. This shift in gene expression seems to enhance the nervous-system-deprived animal’s ability to sense and respond to environmental signals.

This finding, which has implications for research into evolutionary mechanisms and the development of neurodegenerative diseases, appeared November 23 in Philosophical Transactions of the Royal Society, in an article entitled, “Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells.” This article was produced by a group of scientists at the University of Geneva led by Brigitte Galliot, Ph.D., professor of genetics and evolution.

The scientists compared gene expression at various positions along the body axis in polyps devoid or not of their nervous stem cells. They observed a modification of the genetic program in animals depleted of these cells.

“We identified 25 overexpressed genes in epithelial cells, the cells forming the Hydra‘s coating tissues,” said Yvan Wenger, Ph.D., co-first author of the article. “Some of these genes are involved in diverse nervous functions, such as neurogenesis or neurotransmission.”

“[Epitheliomuscular] cells seemingly enhance their sensing ability when neurogenesis is compromised,” the authors of the article explained. “This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.”

Studying Hydra‘s cellular plasticity may be relevant in the context of neurodegenerative diseases. Indeed, some of the genes identified in this animal play an important role in cellular reprogramming or in neurogenesis in mammals. The researchers therefore wonder: would it be possible to restore sensing or secretion functions from other cell types, when some neurons degenerate?

This study points back to the origins of nervous systems. Epithelial cells most probably preceded nerve cells, performing some of their functions, although in a much slower way.

“The loss of neurogenesis in Hydra may provide an opportunity to observe a reverse evolutive process, because it sheds light on a repressed ancestral genetic toolkit. An atavism of epithelial cells, when they most probably also possessed proto-neuronal functions.” concluded Dr. Galliot.