# THE MOLECULAR REGULATORY MECHANISM OF TOOTH ROOT DEVELOPMENT

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $524,469

## Abstract

PROJECT SUMMARY / ABSTRACT
The tooth root is critical for the function of our dentition because it anchors the tooth to the maxilla or mandible.
In addition, the root helps transmit and balance occlusal forces through periodontal ligaments to the jaw bones
and serves as a passageway for the neurovascular bundle that supplies blood flow, nutrition, and sensation to
our teeth. Importantly, tooth root defects resulting from developmental malformations, pathological conditions
and dental treatments are common and significantly compromise quality of life. However, currently we have
limited information on the molecular and cellular regulatory mechanisms of crown-to-root transition and tooth
root development. Significantly, we have recently identified epithelial and mesenchymal stem cells that are
crucial for root development. BMP-mediated SHH signaling provides a niche for Sox2+ epithelial stem cells in
molar root development. Moreover, our preliminary study indicated that BMP-mediated HH and FGF signaling
in the epithelium may control the crown-to-root transition. We have identified Gli1+ cells as the dental
mesenchymal stem cells responsible for controlling root development. In parallel, our preliminary results
demonstrate that an epigenetic regulator Ezh2 modulates the transcriptional activity of key genes in the WNT
and FGF pathways that are involved in regulating epithelial-mesenchymal interactions to control root formation.
We have designed studies to test the hypothesis that BMP-mediated SHH, WNT and FGF signaling control the
fate of epithelial and mesenchymal stem cells during root development. This signaling network and Ezh2 exert
their functional specificity by regulating specific transcription factors and epithelial-mesenchymal interactions to
control root patterning and development. Our Specific Aims are: (1) to examine how epithelial SHH and FGF,
acting downstream of BMP signaling, control the fate of dental epithelial stem cells during root development; (2)
to investigate the functional significance of WNT and FGF signaling in regulating specific transcription factors
and the fate of CNC-derived MSCs during root development. We will elucidate the molecular mechanism(s) by
which signals from the dental mesenchyme control root furcation and development; and (3) to investigate how
Ezh2 controls the fate of CNC-derived MSCs during root development. We will investigate the Ezh2-mediated
molecular signaling mechanism in regulating tissue-tissue interactions to control root patterning and
development.

## Key facts

- **NIH application ID:** 9894789
- **Project number:** 5R01DE022503-07
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Yang Chai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $524,469
- **Award type:** 5
- **Project period:** 2012-07-19 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894789

## Citation

> US National Institutes of Health, RePORTER application 9894789, THE MOLECULAR REGULATORY MECHANISM OF TOOTH ROOT DEVELOPMENT (5R01DE022503-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894789. Licensed CC0.

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