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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

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. 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 AS 602801 (Bentamapimod) 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 AS 602801 (Bentamapimod) size. c-Fos deletion also affected taste cell turnover as obvious 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. The sense of taste is used to recognize food items for consumption while avoiding potentially toxic compounds. To maintain functionality, the peripheral taste cells located in the oral cavity are continuously replaced throughout an organism’s lifetime. If this renewal process is damaged, the ability to taste AS 602801 (Bentamapimod) is usually impaired which negatively affects appetite and can lead to malnutrition. 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 Studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, but how these cells repopulate taste buds is not well understood.4 Very few regulatory factors of taste cell proliferation or differentiation have been identified. Sonic hedgehog (Shh) and Wnt/-catenin signaling pathways have been shown to have an important role in adult taste cell renewal5, 6 and -catenin activity in the taste buds of 6-month-old mice was significantly lower when compared with activity levels in 10-week-old mice.6 Wnt/-catenin signaling has a well-established role in cell proliferation and differentiation in embryonic taste epithelium7 and their role in taste cell turnover may be reminiscent of their function during development. However, the underlying mechanisms affected by Wnt signaling in adult taste cells are unclear. In general, there is very little information about the specific factors and pathways that are required to maintain adult taste cell function. In this study, we have used an unbiased approach of sequencing messenger RNA (mRNA) isolated from taste receptor cells of the circumvallate (CV)/foliate (Fol) taste papillae to identify factors with a potential role in taste cell maintenance. We decided that the expression of the activator protein-1 (AP1) family of transcription factors (c-Fos, c-Jun and Fosb) significantly decreased in the 6 month taste cells compared with the 2 2 month taste cells. c-Fos couples with members of the Jun family to form AP1 transcription activator proteins which have functions in Prom1 cell differentiation, proliferation and death.8, 9, 10 c-Fos is also 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 usually transient and is a response to external stimuli.11, 12 c-Fos is required for normal development11, 13 and is involved in programmed cell death, though this role appears to vary by cell type.14, 15 All of these known functions of c-Fos indicate that it could have an important role in the renewal process of the peripheral taste cells. Using a conditional c-Fos knockout mouse, we found that selectively knocking out c-Fos expression in taste buds caused a degeneration of their structure due to AS 602801 (Bentamapimod) a reduction in both cell proliferation and an increase in apoptosis. Our data identify a new role for c-Fos as a critical regulator of cell AS 602801 (Bentamapimod) maintenance which is unique from its previously recognized functions in other cell types. Results Global mRNA expression changes between 2 and 6-month-old mouse taste cells Our current understanding of the processes that regulate taste cell renewal is limited by the lack of a comprehensive analysis of the genome-wide transcriptional changes that occur in the taste cells during the mouse lifespan. To identify the.