# Mechanisms of Secondary Cartilage Induction and Maintenance in the Jaw

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $396,250

## Abstract

PROJECT SUMMARY
With the goal of devising innovative therapies to treat birth defects, diseases, and injuries that compromise the
function of the temporomandibular joint (TMJ), much needs to be done to uncover mechanisms that direct the
differentiation of secondary cartilage. Secondary cartilage arises after development of the primary cartilaginous
skeleton and plays a critical kinetic role in the articulations and muscle attachments of the jaw. In humans,
secondary cartilage that forms at the condylar and coronoid processes of the mandible is required for normal
function of the TMJ. Jaw movements and associated forces are necessary to induce and maintain secondary
cartilage, but how biomechanical and molecular signals become integrated to do so remains unclear. To
address this question, we propose a series of experiments that leverage the distinct jaw anatomies of duck and
quail embryos. Much like that found in humans, duck develop a pronounced secondary cartilage at the tendon
insertion of their jaw adductor muscle on the coronoid process. An equivalent secondary cartilage is absent in
quail and other species such as mice. We exploit the fact that duck form this secondary cartilage and focus on
the role of neural crest mesenchyme (NCM), which produces all the cartilages and bones in the jaw skeleton.
NCM also makes muscle connective tissues including ligaments and tendons. In contrast, jaw muscles are
derived from mesoderm. Our published and preliminary studies show that NCM, when transplanted from quail
to duck, generates quail-like pattern in the jaw skeleton and accompanying musculature, which in turn causes
a loss of secondary cartilage on the coronoid process. Moreover, paralyzing muscle or blocking Transforming
Growth Factor-Beta (TGFβ) and Fibroblast Growth Factor (FGF) signaling also inhibits secondary
chondrogenesis on the coronoid process. Thus, we hypothesize that species-specific differences in TGFβ and
FGF signaling, jaw architecture, and mechanical forces promote formation of secondary cartilage on the
coronoid process of duck versus quail. We test our hypothesis with three Specific Aims. In Aim 1, we evaluate
the extent to which TGFβ and FGF signaling are NCM-mediated, and use gain- and loss-of-function
approaches to determine precisely when and where these pathways induce secondary cartilage at the
coronoid process. In Aim 2, we investigate the link between jaw architecture and mechanical forces at the
mandibular adductor using a finite element model derived from geometric and material property studies, and
tested through experimental manipulations. In Aim 3, we block mechanotransduction, modulate embryonic
motility, and combine in vivo and in vitro experiments to understand how the local mechanical environment
regulates molecular programs for secondary cartilage. By investigating the effects of NCM-mediated signaling,
musculoskeletal anatomy, and mechanical forces on the induction of secondary cartilage, this project will offer...

## Key facts

- **NIH application ID:** 9954018
- **Project number:** 5R01DE025668-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** RICHARD A SCHNEIDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2016-07-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954018

## Citation

> US National Institutes of Health, RePORTER application 9954018, Mechanisms of Secondary Cartilage Induction and Maintenance in the Jaw (5R01DE025668-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9954018. Licensed CC0.

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