“Here, we are tackling an emerging question in developmental biology: How do external factors drive organ development?” said Julia Peloggia, Ph.D., a former predoctoral researcher in the Piotrowski Lab and lead author on the current study.

The study, published in Development on October 22, 2024, discovered how precursor cells to neuromast ionocytes can sense specific components in their surroundings that cause them to mature. Ionocytes are specialized cells that control concentrations of ions, more commonly known as electrolytes, like calcium, sodium, and potassium. These ions are key components that transmit electrical signals and regulate water pressure within and between cells, tissues, and organs. Most animals’ body mass largely consists of water, making these ion-sensing cells important.

When ion concentrations decrease, a precursor cell adjacent to the neuromast activates regulatory genes and divides into two cells. Then, the two new cells invade the neuromast and trigger a conserved molecular mechanism to specify their fates. Once mature, neuromast ionocytes assist sensory hair cell function by maintaining a steady state of ion concentrations.

Researchers have known for some time that ionocytes exist in other tissues such as the skin and gills of fish. To characterize how ionocytes respond to environmental signals, zebrafish were reared in water with different concentrations of ions. When the fish were placed in purified water, mature neuromast ionocytes were observed to rapidly accumulate, with the largest response following a depletion in calcium ions. Fluorescent imaging allowed the team to track precursor and mature neuromast ionocytes which, along with techniques to modify gene expression, allowed the researchers to hypothesize that a change in salinity was the prominent driver for neuromast ionocyte development.

“We used more than 10 modifications of the zebrafish embryo aquatic environment to test the role of individual components on neuromast ionocyte development,” said Peloggia. “After just two hours, we could detect new neuromast ionocytes, highlighting just how rapid this adaptive response is.”

“I like to describe the zebrafish laboratory environment as a five-star hotel where every parameter is controlled and every request is accommodated,” said Peloggia. “Thus far, we are missing how changes in their natural environment can influence organ development.”

Like zebrafish, many human tissues depend on ionocytes to regulate ion concentrations. For example, when ionocyte function is compromised in the inner ear, the kidneys, or the tissue that stores sperm cells, this can lead to hearing loss, kidney failure, or infertility, respectively.

Unlike zebrafish, human tissues and the regulatory cells that aid them are difficult to study. Thus, zebrafish present an opportunity to study adaptive behaviors, sensory organ flexibility, and the evolution of cell type diversity that may be essential to survive and thrive in a changing climate.

“Zebrafish neuromast ionocytes display a rapid adaptive response,” said Piotrowski. “With climate change, one could argue that species with higher physiological flexibility, such as zebrafish, will be better able to cope because they have these cells that can respond to changes in salinity while species lacking such cells may suffer.”

“Exactly,” said Peloggia. “I think of this as a tuning dial. Starting from an ideal physiological status, the environment can turn this dial, or tip the balance, and the organism must use whatever mechanisms it can to restore an ideal status. For zebrafish, the ionocytes seem to be helping adjust that dial to regain functional physiology.”

As global temperatures and sea levels rise and ice caps melt, widespread fluctuations in the distribution of salinity are inevitable and may impact Earth’s ecosystem. Animals, particularly those that live in water, need flexible and rapid mechanisms to adjust to and survive dramatic changes in their surrounding salt and nutrient concentrations—from dilution following a monsoon to accumulations during dry spells.

“Animals with different adaptive capacities may find themselves relocating to survive,” said Peloggia. “From an ecological standpoint, climate change and a corresponding redistribution of habitats may be a key driver for how new species arise.”

Additional authors include Mark Lush, Ph.D., Ya-Yin Tsai, and Christopher Wood, Ph.D.

This work was funded by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health (NIH) (award: 1R01DC015488-01A1) and by institutional support from the Stowers Institute for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.