SPLTRAK Abstract Submission

Lingual Epithelium, Hedgehog Signaling, and Taste Organ Homeostasis and Sensory Function

Archana Kumari & Charlotte Mistretta
University of Michigan, , ,

Lingual papilla organs include taste bud and non-gustatory cells in complex epithelia that interact with one another, and with stromal cells and nerves. An orchestrated signaling regulation among all of these cell types is essential to taste organ homeostasis and sensation, and the Hedgehog (Hh) pathway is a known regulator for papilla maintenance. The Sonic Hh ligand is in taste bud cells and Hh-responding, Gli1+ epithelial cells are perigemmal to the taste bud and in the papilla basal epithelium. Other Hh pathway components are in taste and non-taste epithelium. If signaling is inhibited with the cancer drug sonidegib, the Hh-responding, Gli1+ epithelial cells are eliminated, with loss of taste buds and associated Shh; this is accompanied by a pattern of reduced proliferation in basal cells of the apical fungiform papilla and a differentiation defect in the papilla epithelial apex. Nerves remain in the taste papilla core, extending to and into the epithelium. Notably, responses from the taste nerves to chemical stimulation of the tongue are eliminated; however, responses to tongue tactile and cold stimuli are retained.  Thus, with Hh signaling deregulation the taste buds and taste responses are compromised, whereas complex epithelial nerve endings and somatosensory responses are intact. If Hh signaling inhibition is terminated by drug withdrawal, then papilla morphology and taste bud numbers are partially restored. Nerve responses to lingual chemical stimulation return, accompanied by renewed Hh signaling in the taste organ epithelium. Hh signaling cells are reconstituted in papillae with a taste bud and Shh, but not in papillae that remain dysmorphic and lack taste buds. Hh signaling in taste organ epithelium is cell specific, and is necessary for and directly associated with sensory function.
Supported by NIDCD NIH Grant DC014428.