# The Role of TGF-Beta Signaling in Neural Crest-Mediated Jaw Bone Remodeling

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $67,265

## Abstract

PROJECT SUMMARY/ABSTRACT
Proper establishment of jaw length is essential to feeding, breathing, and normal development
of oral-motor skills. The jaw often displays an array of size related abnormalities, including
mandibular hypoplasia, retrognathia, asymmetry, and clefting. Treatment for craniofacial defects
often involves multiple surgical interventions, which is a lengthy, costly, and emotionally and
physically draining process. Prevention for at-risk individuals, however, provides a welcome
alternative. Identifying potential strategies for rescue or regeneration depends on understanding
the developmental processes regulating jaw size. The jaw, along with most of the craniofacial
skeleton, derives from the neural crest mesenchyme (NCM), a transient multi-potent cell
population that arises at the neural plate border. We employ a unique in vivo system to study the
NCM and how it executes molecular and histological programs that establish the size and
shape of the jaw skeleton. Understanding how the NCM accomplishes such a complex task,
and the specific mechanisms that determine jaw length, remain unknown. Our published and
preliminary results suggest that differential regulation of matrix metalloproteinases (Mmps),
Runx2, and Transforming Growth Factor-Beta (TGFβ) in a species-specific manner may
contribute to differences in jaw length. We hypothesize that the NCM differentially regulates
Mmps, Runx2, and TGFβ signaling in a species-specific manner, modulating bone resorption
to generate variations in jaw length. To test our hypothesis, we combine the species-specific
developmental programs of quail and duck in a novel chimeric system. Quail have short
jaws whereas those of duck are relatively long, and quail embryos develop much faster than
duck. Exchanging NCM between quail and duck provides a unique way to manipulate
signaling between donor NCM and adjacent host tissues, and allows discovery of NCM-
dependent processes. In Aim 1, we will determine the extent to which the NCM-mediates
Mmps to regulate jaw size. In Aim 2, we will ascertain whether jaw size is affected by
differential regulation of NCM-mediated Runx2 expression. In Aim 3, we will determine the
extent to which NCM mediates jaw length through TGFβ signaling. We will employ gain- and
loss-of-function strategies to understand how changes in bone formation and resorption,
and how TGFβ can regulate Runx2 and Mmp expression to affect jaw length. Each Specific
Aim is clinically relevant and may identify molecular therapies that can be used to
manipulate jaw length. We are confident that our research will provide a foundation for
biologically-based, non- surgical methods to treat disorders of the human jaw.

## Key facts

- **NIH application ID:** 9982684
- **Project number:** 5F32DE027283-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Spenser Scott Smith
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,265
- **Award type:** 5
- **Project period:** 2018-09-15 → 2021-08-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982684

## Citation

> US National Institutes of Health, RePORTER application 9982684, The Role of TGF-Beta Signaling in Neural Crest-Mediated Jaw Bone Remodeling (5F32DE027283-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9982684. Licensed CC0.

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