A recent study explores the intricate communication between nerve cells and muscle cells through electrical signals during development, referred to as bioelectricity. This communication is essential for the proper development and behavior of organisms. The research identifies specific genes responsible for regulating this process and sheds light on the consequences of any malfunctions. The findings offer valuable insights into the genetic factors behind muscle disorders in humans.
After four decades, a longstanding question in the field of biology has been finally answered, all thanks to an unexpected discovery involving a zebrafish unable to move its tail.
A fresh study from the University of Oregon delves into the communication between nerve and muscle cells through electrical signals, a phenomenon known as bioelectricity.
This communication occurs through specialized channels connecting cells, playing a crucial role in proper development and behavior. The study identifies specific genes that govern this process and delineates the implications of any disruptions.
These findings not only provide insights into the genetic basis of muscle disorders in humans but also address long-standing queries in developmental biology.
Judith Eisen, a neuroscientist at UO, who had observed a peculiar communication pattern among zebrafish muscle cells in the 1980s, expressed her joy at finally unraveling this mystery: “This is something many of us have wondered about for many, many years — and now we’ve figured it out!”
Eisen and her team have documented their discoveries in a paper published in Current Biology.
The research effort solidifies the work of three generations of UO neuroscientists and serves as a reminder to all researchers of the importance of meticulous record-keeping. Eisen stumbled upon her original laboratory notebooks when relocating to a temporary lab during a building renovation a few years back. Her inked sketches and abbreviated notes from years ago proved to be relevant even today.
Unraveling a muscular enigma
In 1983, Eisen, as a postdoctoral researcher under Monte Westerfield at UO, embarked on her scientific journey, exploring zebrafish as a new model organism. The aim was to leverage these shimmering fish to investigate vertebrate animal development.
Zebrafish, sharing numerous genes with humans, proved to be a valuable addition to biological research, offering insights into the genetic foundations of human ailments. Moreover, the transparent embryos of zebrafish enable real-time observation of development under a microscope.
However, at that time, much of the zebrafish system was uncharted territory, requiring biologists to decipher the care of these fish in a lab setting and effectively use them for experiments.
During an experiment using a yellow tracing dye to highlight nerve cells in zebrafish, Eisen and Westerfield noticed an intriguing pattern as the dye spread through muscle cells. The manner in which it spread suggested direct cell-to-cell communication through specialized channels, a departure from the conventional understanding of muscle cell communication.
Though the existence of such communication channels was known, at that time, a lack of knowledge about the genes governing this process hampered further exploration, leading to a standstill in research.
Despite the dead end, Eisen made significant contributions to developmental biology over her career and was recently inducted into the National Academy of Sciences.
Over the past four decades, Eisen and her UO colleagues, together with researchers worldwide, have continued to enhance the zebrafish as a model organism, aided by advancements in genetic technologies.
A zebrafish anomaly
Several years later, Eisen’s observation caught the attention of Adam Miller, a UO neuroscientist exploring cell-to-cell communication through electrical signals. Miller’s team focuses on neural circuitry formation and behavior, including the study of gap junctions, physical conduits enabling direct electrical communication between cells crucial for early developmental processes.
Zebrafish serve as an ideal species for investigating electrical communication due to their transparent embryos, facilitating the real-time visualization of electrical flow through cells.
While researching zebrafish with gap junction mutations, a team member, Rachel Lukowicz-Bedford, identified a zebrafish displaying abnormal tail movements. Further experiments revealed that this fish could be a link to Eisen’s 1980s muscle cell observation.
In healthy zebrafish, the researchers observed electrical signals traveling through gap junctions between muscle cells. However, in zebrafish with mutations, these signals were disrupted, leading to improper muscular development characterized by crinkly muscle fibers.
The team attributed this change to a mutation in a specific gene, demonstrating that the gene plays a role in creating the channels that allow nervous system coordination of early muscle activity. Insufficient electrical signaling during development led to disorganized muscle fibers, resulting in severe muscle defects.
The finding clarified the mystery recorded by Eisen in her lab notebook years ago, highlighting the significance of these communication channels in muscle development.
These findings not only offer insights into muscle development in humans but also emphasize the critical role of electrical signaling in inter-organ communication during development, suggesting broader implications for understanding human diseases.
“The gene we studied in this paper is not a peculiar zebrafish gene; it exists in humans as well,” Lukowicz-Bedford explained. “By studying zebrafish, we can delve into the functions of this gene in humans and unravel its mysteries. We have uncovered the elusive function of a gene that was previously unknown.”
The research underscores the importance of electrical signaling between different biological systems for development and adult functions. The researchers propose that similar communication mechanisms likely play a role in the development of other bodily systems, not limited to muscles.
“Understanding the genes enabling this inter-system bioelectricity flow, comprehending their mechanisms, and identifying the consequences of communication disruptions will provide new insights into human diseases,” Miller emphasized.
