# Dental Follicle: A Central Regulator of Tooth Root Formation and Regeneration

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $363,090

## Abstract

PROJECT SUMMARY/ABSTRACT
The tooth root is a critical component of the tooth, anchored to surrounding alveolar bones through the
periodontal ligament (PDL). Appropriate formation of the root and its surrounding structure is essential not only
for fundamental functions of the tooth in mastication for nutrition intake, but also for growth and development of
the lower face. Prevalent dental diseases such as caries and periodontal diseases are the etiology for tooth
loss, which can be treated only by prostheses lacking functional structures, leading to compromised long-term
prognosis. An effective approach to regenerate a functional periodontal attachment apparatus is needed to
achieve a breakthrough in dental regenerative therapies. During tooth root formation, the dental follicle (DF)
provides precursor cells for cementoblasts, periodontal ligament (PDL) cells and alveolar cryptal bone
osteoblasts to establish the functional periodontal attachment apparatus, the periodontium. Currently, how
diverse populations of dental root mesenchymal progenitor cells work together and generate highly functional
tooth roots remains unknown. In this proposal, we will define how concerted actions of distinct classes of
dental root mesenchymal progenitor cells are essential for proper formation and regeneration of the tooth root
accompanied by a functional periodontal attachment apparatus. In Aim 1, we will define how Hedgehog-Fox
pathway regulates DF mesenchymal progenitor cells. We hypothesize that the Forkhead (Fox) transcription
factors play a key role in regulating physiological functions of Hedgehog-responsive DF mesenchymal
progenitor cells. We will first reveal the diversity of Hedgehog-responsive Gli1+ DF cells using single cell RNA-
seq analyses, and determine their relationships with PTHrP+ DF cells and other precursor cell populations.
Second, we will determine the function of Gli1+, PTHrP+ and Runx2+ cells in periodontium formation using
inducible cell ablation experiments, and further test the function of Foxf1 and Foxf2 in periodontium formation
using their floxed alleles. In Aim 2, we will identify Wnt-mediated roles of apical root mesenchymal progenitor
cells in tooth root formation. We hypothesize that chemokine (C-X-C motif) ligand 12 (CXCL12)+ mesenchymal
progenitor cells in the apical root area orchestrate formation of the tooth root and the apical periodontium in a
canonical Wnt signaling-mediated manner. We will determine the relationship between CXCL12+ cells and
stem cells for apical papilla (SCAP) using ex vivo culture system, and define molecular mechanisms underlying
a Wnt-mediated cell fate choice of mesenchymal progenitor cells by a comparative RNA-seq analysis followed
by in situ validation. In Aim 3, we will determine actions of dental root mesenchymal progenitor cells in
periodontal regeneration. We hypothesize that distinct classes of dental root mesenchymal progenitor cells
contribute to regeneration in a concerted manner. We will ...

## Key facts

- **NIH application ID:** 10763435
- **Project number:** 5R01DE029181-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Wanida Ono
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $363,090
- **Award type:** 5
- **Project period:** 2022-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763435

## Citation

> US National Institutes of Health, RePORTER application 10763435, Dental Follicle: A Central Regulator of Tooth Root Formation and Regeneration (5R01DE029181-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10763435. Licensed CC0.

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