Abstract
The sense of taste is used by organisms to achieve the optimal nutritional requirement and avoid potentially toxic compounds. In the oral cavity, taste receptor cells are grouped together in taste buds that are present in specialized taste papillae in the tongue. Taste receptor cells are the cells that detect chemicals in potential food items and transmit that information to gustatory nerves that convey the taste information to the brain. As taste cells are in contact with the external environment, they can be damaged and are routinely replaced throughout an organism's lifetime to maintain functionality. However, this taste cell turnover loses efficiency over time resulting in a reduction in taste ability. Currently, very little is known about the mechanisms that regulate the renewal and maintenance of taste cells. We therefore performed RNA-sequencing analysis on isolated taste cells from 2 and 6-month-old mice to determine how alterations in the taste cell-transcriptome regulate taste cell maintenance and function in adults. We found that the activator protein-1 (AP1) transcription factors (c-Fos, Fosb and c-Jun) and genes associated with this pathway were significantly downregulated in taste cells by 6 months and further declined at 12 months. We generated conditional c-Fos-knockout mice to target K14-expressing cells, including differentiating taste cells. c-Fos deletion caused a severe perturbation in taste bud structure and resulted in a significant reduction in the taste bud size. c-Fos deletion also affected taste cell turnover as evident by a decrease in proliferative marker, and upregulation of the apoptotic marker cleaved-PARP. Thus, AP1 factors are important regulators of adult taste cell renewal and their downregulation negatively impacts taste maintenance.
Highlights
The sense of taste is used to identify food items for consumption while avoiding potentially toxic compounds
The efficiency of the taste cell renewal process decreases with age and can be disrupted by disease, radiation or chemotherapy which all results in taste loss or dysfunction.[1,2,3]
Sonic hedgehog (Shh) and Wnt/β-catenin signaling pathways have been shown to have an important role in adult taste cell renewal[5,6] and β-catenin activity in the taste buds of 6-monthold mice was significantly lower when compared with activity levels in 10-week-old mice.[6]
Summary
The sense of taste is used to identify food items for consumption while avoiding potentially toxic compounds. C-Fos couples with members of the Jun family to form AP1 transcription activator proteins which have roles in cell differentiation, proliferation and death.[8,9,10] c-Fos is a well-established early response gene that transduces short-term stimuli into long-term responses within a cell In this role, the expression of c-Fos is transient and is a response to external stimuli.[11,12] c-Fos is required for normal development[11,13] and is involved in programmed cell death, though this role appears to vary by cell type.[14,15] All of these known roles of c-Fos indicate that it could have an important role in the renewal process of the peripheral taste. Our data identify a new role for c-Fos as a critical regulator of cell maintenance which is unique from its previously identified roles in other cell types
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