# Regulation of connective tissue in the cell renewal of mature taste buds

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2024 · $379,862

## Abstract

Project Summary/Abstract
 Mammalian taste buds are a cluster of specialized epithelial cells residing primarily in the epithelium of the
lingual taste papilla which covers a core of connective tissue. Like other epithelial cells, taste bud cells have a
short lifespan and undergo continuous renewal. Therefore, the homeostasis of taste buds and taste sensation
requires constant taste bud cell differentiation from progenitors. Thorough information of the regulation in taste
cell differentiation from progenitors is essential to understanding taste disorders and finding effective therapeutic
treatments. Prior studies on the molecular regulation in taste cell differentiation have focused on the signals
within epithelium. Little is known regarding the roles of the underlying connective tissue.
 Recently, for the first time in the field, our findings demonstrated the requirement of signals from neural crest-
derived tongue mesenchyme in taste papilla differentiation during embryonic development. This leads us to ask
whether the underlying connective tissue regulates the cell renewal of mature taste buds in adult animals. Our
preliminary data revealed that delivery of extracted proteins from the genetically modified embryonic tongue
mesenchyme into adult mouse tongue resulted in an alteration of taste buds in the injection-surrounding tongue
region. Moreover, selected signaling proteins (i.e., Noggin and Pleiotrophin) secreted by embryonic tongue
mesenchyme were also detected in the neural crest-derived connective tissue cells from adult mouse tongue,
suggesting a mesenchymal regulation in the homeostasis of taste buds in adult mice.
 We hypothesize that in adult animals the neural crest derived connective tissue cells in the core of taste
papillae send signals to the overlying epithelium and regulates cell renewal of mature taste buds. In this proposal,
we will use both in vivo and ex vivo systems to examine the effects of cell products from connective tissue cells
on taste cell differentiation. Neural crest-derived connective tissue cells in fungiform and circumvallate papilla
region will be sorted from adult Sox10-Cre/tdTomato (tdT) mice. The tdT+ (neural crest-derived) cells will be
cultured for isolation of protein fractions (>100 kDa, 10-100 kDa, <10 kDa) from conditioned medium. The effects
of cell products on taste cell differentiation will be tested in adult Krt5-CreER/nTnG and Shh-CreER/nTnG mice
in which taste bud progenitors (Krt5+) and precursors [sonic hedgehog (Shh)+], and derived taste cells are traced.
 In Aim 1, we will test in vivo whether homeostasis of mature fungiform taste buds is regulated by the products
of neural crest-derived connective tissue cells using hydrogel to deliver the fractions of connective tissue cell
products and two individual proteins (Noggin and Pleiotrophin) into the subepithelial space of tongue tip. In Aim
2, we will test whether circumvallate taste cell differentiation is regulated by the underlying connecti...

## Key facts

- **NIH application ID:** 11047309
- **Project number:** 1R21DC022451-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Hongxiang Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $379,862
- **Award type:** 1
- **Project period:** 2024-09-19 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11047309

## Citation

> US National Institutes of Health, RePORTER application 11047309, Regulation of connective tissue in the cell renewal of mature taste buds (1R21DC022451-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11047309. Licensed CC0.

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