# Modular control of jaw tendon specification by the Nr5a2 orphan nuclear receptor

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $379,779

## Abstract

Project Summary
In order for the jaw to properly function, the jaw skeleton must be integrated to the underlying muscles through
tendons. The prevalence of tendon injuries is high and in some cases can contribute to temporomandibular
joint disorders, yet both the development and repair of tendons are largely understudied. The skeleton and
tendons of the jaw are derived from cranial neural crest cells (CNCCs), in contrast to the skeleton and tendons
of the fins/limbs and spine that are derived from mesoderm. Do tendons derived from different lineages depend
on similar or distinct upstream signals for their specification? This proposal tests the innovative idea that
tendon specification is modular, with head- and trunk-specific transcription factors initiating tendon
development through head- and trunk-specific enhancers of critical tenocyte factors such as Scleraxis. By
conducting single-cell RNA expression profiling of CNCC derivatives in the developing zebrafish face, we have
found that expression of the nr5a2 orphan nuclear receptor marks cells along a developmental trajectory
toward jaw tendon fate. Utilizing mutant and transgenic zebrafish models, we find that Nr5a2 is necessary and
sufficient for specification of jaw tendon at the expense of cartilage fates. In addition, by assaying open
chromatin indicative of active enhancers in CNCCs, as well as head versus trunk tenocytes, we find a number
of putative head- and trunk-specific enhancers of scleraxis-a. In this proposal, we use transgenic and cutting-
edge genomics techniques to test that Nr5a2 directly binds and activates jaw-specific scleraxis-a enhancers.
We also use conditional genetics in mouse to test that Nr5a2 has a conserved role in specifying jaw and
middle ear tendons derived from the mandibular arch in mammals. Completion of these aims will reveal the
regulatory logic by which tendons are specified in different parts of the body, as well as a highly specific role for
the Nr5a2 orphan nuclear receptor in promoting jaw tendon formation.

## Key facts

- **NIH application ID:** 10115696
- **Project number:** 5R21DE029656-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Gage D Crump
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,779
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115696

## Citation

> US National Institutes of Health, RePORTER application 10115696, Modular control of jaw tendon specification by the Nr5a2 orphan nuclear receptor (5R21DE029656-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115696. Licensed CC0.

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