Year: 2016
Type: article
Abstract: For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings suggest that taste alterations in cancer patients using systemic Hedgehog pathway inhibitors result principally from interruption of signaling activity in taste papillae.
Source: PLoS Genetics
Institution: University of Michigan
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: University of Michigan, National Institutes of Health, College of Pharmacy, University of Michigan, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: STUDIES ON THE USE OF STRAP MUSCLES IN CONSONANT VOICING, G1586298813, G1614961855, G2490765859, G255086095, G2730293317, Molecular Regulation of Hair Follicle Morphogenesis, G3375085838, G3459705427, G4430766893, G496050054, G5520316217, Kinesin-2 Regulation of GLI Function in Hedgehog Signal Transduction, Reversing Diabetic Peripheral Neuropathy Through Exercise, G6384846191, G6399161982, Dosage-Dependent Hedgehog Signaling in Pancreatic Cancer, The Role of Cilia in Regulating Olfactory Horizontal Basal Cells, Development of the Sense of Taste, Hedgehog signaling in maintaining taste organ structure and function: basic and clinical studies, G9000207620, University of Michigan Rogel Cancer Center Support Grant 2023-2028
OpenAlex ID: W2557574279