Taste sensation on the anterior tongue requires chorda tympani nerve function and connections with continuously renewing taste receptor cells. However, it is unclear which signaling pathways regulate the receptor cells to maintain @entity1109 . Hedgehog (HH) signaling controls cell proliferation and differentiation in numerous tissues and is active in taste papillae and taste buds. In contrast, uncontrolled HH signaling drives tumorigenesis, including the common @entity1489 , @entity1491 ( @entity1491 ). Systemic HH pathway inhibitors (HPIs) lead to @entity1491 regression but these drugs cause severe taste disturbances. We tested the hypothesis that taste disruption by HPIs reflects a direct requirement for HH signaling in maintaining taste organs and gustatory sensation. In @entity19 treated with the HPI @entity40634 up to 28 days, HH-responding cells were lost in @entity1829 epithelium and papillae acquired a conical apex. Taste buds were either absent or severely reduced in size in more than 90% of aberrant papillae. Taste bud remnants expressed the taste cell marker @entity14436 and papillae retained expression of nerve markers, neurofilament and @entity57762 . Chorda tympani nerve responses to taste stimuli were markedly reduced or absent in @entity40634 -treated @entity19 . Responses to touch were retained, however, whereas cold responses were retained after 16 days of treatment but lost after 28 days. These data identify a critical, modality-specific requirement for HH signaling in maintaining taste papillae, taste buds and neurophysiological taste function, supporting the proposition that taste disturbances in HPI-treated @entity1 are an on-target response to HH pathway blockade in taste organs.

Hedgehog pathway blockade with the cancer drug XXXX disrupts taste organs and taste sensation.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity40634 :: ('MESH:C561435', 'Chemical') :: ['LDE225'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1489 :: ('MESH:D012878', 'Disease') :: ['skin cancer'] @entity14436 :: ('16691(Tax:10090)', 'Gene') :: ['Keratin 8'] @entity1109 :: ('MESH:D012678', 'Disease') :: ['chorda tympani sensation'] @entity1829 :: ('MESH:D010211', 'Disease') :: ['fungiform papilla'] @entity1491 :: ('MESH:D002280', 'Disease') :: ['basal cell carcinoma', 'BCC'] @entity57762 :: ('228139(Tax:10090)', 'Gene') :: ['P2X3']
@entity40634 :: (MESH:C561435,Chemical) :: ['LDE225']
