# Investigating the role of Gli activator in development of the murine mandibular prominence

> **NIH NIH F31** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $31,820

## Abstract

Project Summary/Abstract
Irradiation-induced hyposalivation and irreversible submandibular gland (SMG) and tongue
damage are among the most common and harmful side-effects of radiation therapy during
treatment for head and neck cancers. Patients with irreversible hyposalivation must live with a
plethora of side-effects including: consistent dry mouth, tooth-decay, inflammation, fungal
injection, and problems chewing and swallowing. A more complete understanding of the
development of the SMGs and tongue is necessary for devising more effective regenerative
strategies for these patients. This proposal aims to elucidate the molecular mechanisms involved
in early SMG and tongue development. Specifically, I will examine Sonic Hedgehog (Shh)-
dependent mechanism of spatially defined transcriptional networks in the mandible to initiate both
SMG and tongue development. Shh signaling is transduced via the Gli transcription factors, which
can be processed into transcriptional activators (GliA) or repressors (GliR). This proposed work
focuses on understanding how Gli interaction with co-factors and the downstream effects of Gli-
mediated Shh signaling contribute to development of tissues within the mandibular prominence.
Specifically, in Aim 1 I will ask if GliA requires co-factor activity to initiate spatially restricted
transcriptional networks in the developing mandibular prominence with the hypothesis that Hand2
functions as a GliA co-factor to induce glossal transcriptional networks. In Aim 2, I will ask if Gli-
dependent transcription is necessary for controlling epithelial proliferation and branching
morphogenesis of the SMG tubules by testing the hypothesis that GliA directly activates Nrg2 in
the SMG to induce epithelial proliferation and initiate branching morphogenesis. We aim to
investigate the dynamic roles of Shh signaling by conditionally knocking out GliA activity and
perturbing Hand2 expression in mandibular tissues. Altogether, this study is important for
advancing our understanding of the complex molecular dynamics of SMG and tongue
development. Understanding these complex processes can influence future methods for
developing regenerative therapies for head and neck cancer patients who experience irreversible
radiation-induced SMG and lingual damage.

## Key facts

- **NIH application ID:** 9820688
- **Project number:** 5F31DE027872-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Kelsey Elliott
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,820
- **Award type:** 5
- **Project period:** 2018-12-01 → 2020-08-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9820688

## Citation

> US National Institutes of Health, RePORTER application 9820688, Investigating the role of Gli activator in development of the murine mandibular prominence (5F31DE027872-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9820688. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*