# Mesenchyme-Dependent Epithelial Signals That Promote Osteogenesis In the Jaw

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $51,836

## Abstract

PROJECT SUMMARY
The formation of bone in the mandible requires that neural crest mesenchyme (NCM) undergoes an inductive
interaction with adjacent epithelium. This interaction relies on a number of yet to be identified signals that permit
the NCM to differentiate into bone. Thus, identifying molecular signals mediating this epithelial-mesenchymal
interaction (EMI) would allow us to discover proteins that regulate mandibular osteogenesis, and which
potentially could be used therapeutically to generate bone in cases of disease and injury. One signaling molecule
currently known to participate in these EMI and promote osteogenesis in the jaw is BMP4. However, BMP4 alone
is not sufficient to generate bone in mandibular mesenchyme cultured without adjacent epithelium. The overall
goal of this project is to identify other osteoinductive signals and test if they can be used in combination with
BMP4 to function in place of the epithelium that normally induces bone in the jaw. An RNA-seq experiment and
preliminary data reveal that spatiotemporal changes in several candidate genes including members of the WNT
and CXC signaling pathways are present at the right time, place, and levels to mediate the osteogenic EMI in
the mandible. This project will investigate the role of these genes and test the extent to which they govern the
EMI required for bone formation in the mandible. The strategy employs a unique avian chimeric system and
involves transplanting NCM, which generates all of the osteogenic precursor cells in the mandible between quail
and duck embryos. Aim 1 will characterize the spatiotemporal expression of these genes qualitatively and
quantitatively on the mRNA and protein levels, and test if their expression is mediated by NCM. Aim 2 will use
in vitro organ culture and tissue recombinations to test if expression of these genes in mandibular mesenchyme
requires epithelial signaling. Aim 3 will employ gain- and loss-of-function approaches to identify the role of these
genes and test if these genes regulate the timing of mandibular osteogenesis and if can they induce bone when
administered either alone or in various combinations with BMP4 in the absence of mandibular epithelium. This
project will lead to the discovery of in vivo mechanisms through which NCM controls bone formation in the jaw
skeleton and has clinical relevance by testing the efficacy of specific molecules that could ultimately be used
therapeutically to benefit human patients. Completion of this fellowship will provide the scientific and technical
training necessary for advancing the career of a dentist-scientist studying craniofacial development.

## Key facts

- **NIH application ID:** 10444916
- **Project number:** 5F30DE027616-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** An Nhat Duy Nguyen
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,836
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444916

## Citation

> US National Institutes of Health, RePORTER application 10444916, Mesenchyme-Dependent Epithelial Signals That Promote Osteogenesis In the Jaw (5F30DE027616-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10444916. Licensed CC0.

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