Scientists have discovered a key protein that allows the sensory cells responsible for detecting sweetness to survive nerve damage, a finding that helps solve a long-standing mystery about taste bud resilience. Researchers found that a protein called c-Kit, present in sweet-sensing taste cells, makes them uniquely resistant to the degeneration that typically follows neural injury. This mechanism not only preserves the sense of sweetness but is also essential for the subsequent regeneration of the entire taste bud, ensuring that other taste functions can be restored.
Taste buds are fundamentally dependent on the nerves that connect them to the brain for their survival and function. When these nerves are damaged, taste buds usually deteriorate, leading to a loss of taste. Although it was known that taste buds could regenerate once the nerves regrow, the cellular process that supported this recovery was poorly understood. The new research, led by scientists at Korea University College of Medicine, reveals that a specific subset of taste cells—those that sense sweetness—act as durable anchors, weathering the injury and guiding the rebuilding process for the other cell types responsible for salty, sour, bitter, and umami tastes.
Unraveling Taste Bud Resilience
For decades, sensory neuroscientists have worked to understand the relationship between taste cells and the nerves they rely on. The prevailing model showed that severing the connection to the brain, a process known as denervation, leads to the rapid death of most taste bud cells. Yet, clinical and experimental observations hinted that not all taste perception was lost equally and that the system could eventually bounce back. This suggested a more complex cellular response to injury than was previously understood. The central question was how a sensory organ so reliant on neural input could recover its full function after a significant disruption.
The study, published in the International Journal of Oral Science, addresses this question by identifying the specific cell type that withstands the damage. Researchers Dr. Dong-Hoon Kim and Professor Yong Taek Jeong demonstrated that while most taste cells degenerate after nerve injury, sweet-sensing cells that express the c-Kit protein exhibit remarkable durability. This discovery clarifies that the regeneration of taste buds is not a spontaneous event but is actively supported by a resilient population of surviving cells that serve as a foundation for regrowth.
The Pivotal Role of C-Kit Signaling
The investigation pinpointed c-Kit signaling as the core mechanism behind the sweet cells’ survival. The c-Kit protein is a type of receptor tyrosine kinase, a class of proteins involved in cellular signaling pathways that govern cell growth, differentiation, and survival. In the context of taste buds, this signal appears to provide an intrinsic survival advantage to sweet cells, allowing them to persist even when the external support from nerves is withdrawn. This finding explains the observation that the ability to taste sweetness often persists longer than other tastes when nerve function is compromised.
To confirm that c-Kit was the critical factor, the research team conducted experiments using a drug called imatinib, also known as Gleevec, which is a cancer therapy drug that functions by blocking c-Kit signaling. When this inhibitor was administered, the otherwise resilient sweet taste cells disappeared following nerve damage. Furthermore, their disappearance prevented the re-emergence of the other types of taste cells, effectively halting the entire regeneration process. This demonstrated conclusively that the c-Kit pathway is indispensable for both the survival of sweet cells and the broader reconstruction of the taste bud.
Advanced Models Confirm the Mechanism
Experiments in Animal and Organoid Models
The researchers used a combination of sophisticated models to validate their findings. They performed nerve transection procedures in mice to create a reliable injury model, which allowed them to observe the cellular response over time. These experiments showed that two weeks after the injury, the c-Kit-expressing sweet cells were the predominant survivors in the taste buds. By the four-week mark, the presence of these surviving cells directly correlated with the regeneration of other taste cell types.
In addition to live animal models, the team used taste bud organoids, which are three-dimensional cell cultures grown in a lab that mimic the structure and function of actual taste buds. These organoids allowed the scientists to study the cells in a controlled environment, free from other biological variables. In the organoid cultures, the sweet cells continued to grow even when essential survival factors were removed from their environment, confirming their autonomous resilience. However, just as in the animal models, applying the c-Kit inhibitor imatinib caused these robust cells to die off.
A Coordinated Cellular Recovery Effort
While the c-Kit-expressing sweet cells are the heroes of the regeneration story, the research revealed they do not act alone. The study also identified a secondary mechanism that contributes to the repair of the tissue surrounding the taste buds. A different population of cells, known as Type III cells, was observed acquiring stem-like properties after the nerve injury. These cells helped repair the epithelial lining around the taste buds, creating a stable environment for the sensory organ to rebuild itself.
This dual process highlights a sophisticated and collaborative recovery system. The c-Kit-positive sweet cells act as the primary drivers of taste cell regeneration, while other supporting cells focus on structural repair. This multi-pronged approach ensures that both the specialized sensory tissue and its surrounding architecture are restored, leading to a more complete and functional recovery of the sense of taste.
New Frontiers in Taste Science and Health
This discovery marks a significant advance in sensory neuroscience, as it is the first to identify a method for selectively controlling a specific type of taste cell. While the research does not offer an immediate treatment for taste disorders, it provides a crucial foundation for future investigations into taste resilience and recovery. Understanding the molecular guardians of taste cells could pave the way for new therapies for patients who have lost their sense of taste due to nerve damage, chemotherapy, or other medical conditions.
In the long term, these findings could have broad applications. A deeper understanding of taste mechanics could guide new approaches to improving nutrition, supporting patients with taste-related difficulties, and advancing flavor science. By uncovering the central role of c-Kit in taste bud regeneration, the study opens up new avenues for both fundamental research and future clinical innovations.