Onset of taste bud cell renewal starts at birth and coincides with a shift in SHH function.

Erin J Golden,Linda A Barlow,G Devon Trahan,Kenneth L Jones,Jennifer K Scott,Timothy J Fellin,Eric D Larson,Lauren A Shechtman,Dany Gaillard

doi:10.7554/elife.64013

Abstract

Embryonic taste bud primordia are specified as taste placodes on the tongue surface and differentiate into the first taste receptor cells (TRCs) at birth. Throughout adult life, TRCs are continually regenerated from epithelial progenitors. Sonic hedgehog (SHH) signaling regulates TRC development and renewal, repressing taste fate embryonically, but promoting TRC differentiation in adults. Here, using mouse models, we show TRC renewal initiates at birth and coincides with onset of SHHs pro-taste function. Using transcriptional profiling to explore molecular regulators of renewal, we identified Foxa1 and Foxa2 as potential SHH target genes in lingual progenitors at birth and show that SHH overexpression in vivo alters FoxA1 and FoxA2 expression relevant to taste buds. We further bioinformatically identify genes relevant to cell adhesion and cell locomotion likely regulated by FOXA1;FOXA2 and show that expression of these candidates is also altered by forced SHH expression. We present a new model where SHH promotes TRC differentiation by regulating changes in epithelial cell adhesion and migration.

Highlights

Taste buds are the primary end-organs of the gustatory system, which reside in 3 types of specialized epithelial papillae on the tongue; fungiform (FFP) in the anterior tongue and circumvallate and foliate, posteriorly
Using inducible lineage tracing we show that non-taste lingual epithelium and taste buds have a common embryonic origin from KRT14+ basal cells, and that once placodes have formed, embryonic KRT14+
We find FOXA2 and FOXA1, in addition to known expression of SOX2, are expressed in and around taste buds at P0 and their expression is altered in response to forced Sonic hedgehog (SHH) expression

Summary

Introduction

Taste buds are the primary end-organs of the gustatory system, which reside in 3 types of specialized epithelial papillae on the tongue; fungiform (FFP) in the anterior tongue and circumvallate and foliate, posteriorly. Regardless of papilla location, each taste bud houses a collection of heterogeneous taste receptor cells (TRCs) that transduce taste stimuli, including sweet, umami, salt, sour, and bitter, to signal palatability, nutritional value and/or danger of substances in the oral cavity. These signals are conveyed from taste buds to the brain via gustatory nerve fibers of the VIIth and IXth cranial nerves. Box transcription factor, is a key regulator of embryonic taste bud formation and adult taste cell renewal, and in both contexts, SOX2 is required for TRC differentiation (Castillo-Azofeifa et al, 2018; Ohmoto et al, 2020; Okubo et al, 2006). We sought to define when TRC renewal from adult progenitors occurs, if this renewal coincides with functional shifts in the response of lingual epithelium to SHH, and identify genetic components, in addition to SOX2, that may function downstream of SHH in TRC renewal

Results

Discussion

876 Supplementary