# Defining gene expression and regulation in lingual taste and non-taste papilla epithelium

> **NIH NIH R21** · ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED · 2021 · $161,000

## Abstract

Abstract
The tongue is a heterogeneous tissue that comprises taste fungiform papillae (FP) and non-taste filiform
papillae (FILIF) in the anterior region. Maintenance of FP and FILIF requires tight regulation of basal epithelial
cell renewal and subsequent proper differentiation. The basal epithelia of FP and FILIF differentiate into distinct
sub-sites of the tongue, suggesting significant differences in gene regulation. Understanding the genes that
regulate the maintenance of these distinct taste and non-taste epithelia will provide fundamental insight into the
mechanisms that control tongue function. Our data establish that Hedgehog (HH) signaling in epithelial cells is
essential for adult FP maintenance. Strikingly, within the epithelium, expression of the HH transcriptional
effector and target gene, Gli1, is restricted to the FP, while the related transcription factor and key HH pathway
component, Gli2 is expressed in the entire basal lingual epithelium, including FP and FILIF. Although we have
demonstrated an essential role for epithelial Gli2 in FP maintenance, there remains a major gap in
understanding how GLI2 regulates FP homeostasis. Further, while essential for many oral functions, non-taste
FILIF homeostasis remains understudied. We hypothesize that FP and FILIF epithelia have distinct gene
profiles that differentially regulate lingual tissue homeostasis. We will use Gli1 reporters to efficiently
distinguish between taste and non-taste epithelia. In Aim 1 we will discover differentially expressed genes and
their regulation by HH signaling in the FP and FILIF epithelial cell populations employing RNA-seq
simultaneously with GLI2 ChIP-seq, using a novel FLAG-tagged knock-in Gli2 allele. Our published data show
that inhibition of HH signaling using the cancer drug sonidegib is sufficient to drive taste organ and sensation
loss whereas the non-taste FILIF remain intact. Notably, patients who take sonidegib report severe taste
dysgeusia and ageusia. Building on studies to understand the mechanisms of taste alteration after
pharmacological inhibition of HH pathway, we will determine deregulated genes and their function. Although
expression of Gli1 is eliminated after sonidegib treatment, our preliminary data indicate that Gli2 expression is
retained in the FP epithelium. In Aim 2, to understand the exact effects of HH pathway blockade and role of
active Gli2 in FP and FILIF, we will rely on similar experimental approaches combining RNA-seq and GLI2
ChIP-seq. The data obtained will help to understand and illustrate mechanisms that underlie taste disruptions
in patients receiving HH pathway inhibitor drugs and may lead to identification of novel targets for development
of therapeutic approaches. Principally, defining gene expression and regulation in the distinct taste
(Gli1+;Gli2+) and non-taste (Gli1-;Gli2+) epithelia will confer advanced knowledge about the mechanisms of
tongue homeostasis. Overall, this proposal will lay the foundation fo...

## Key facts

- **NIH application ID:** 10147026
- **Project number:** 5R21DC017799-04
- **Recipient organization:** ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED
- **Principal Investigator:** Archana Kumari
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $161,000
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147026

## Citation

> US National Institutes of Health, RePORTER application 10147026, Defining gene expression and regulation in lingual taste and non-taste papilla epithelium (5R21DC017799-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147026. Licensed CC0.

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