# Wnt5a/Ror2 Signaling in Jaw Bone Development

> **NIH NIH R03** · UNIVERSITY OF MISSOURI KANSAS CITY · 2022 · $156,500

## Abstract

PROJECT SUMMARY
Our long-term goal is to discover novel molecular-based therapies for regulating the size of bone as a means to
address the need for non-surgical treatments of craniofacial malformations. Little is known regarding the precise
molecular mechanisms controlling jaw size during growth and development. This lack of knowledge leaves
distraction osteogenesis as one of the few available interventions to change jaw size, even though bones of the
face are known to be much more difficult to manipulate with this technique than long bones. Procedures to treat
jaw size disparities will greatly benefit from a broader knowledge base of molecular and cellular mechanisms
that control jaw size. The objective of the current study is to build toward this goal by understanding how the
cranial neural crest (CNC), which forms all the elements in the facial and jaw skeletons, regulates jaw size. To
address this issue, we propose to manipulate in vivo the CNC, a highly accessible embryonic population. For
example, we can transplant quail donor CNC into a duck host, which creates a chimeric quck; and we transplant
duck donor CNC into the quail host, generating chimeric duail. Exploiting the divergent developmental programs
of quail and duck provides a unique way to manipulate signaling between CNC and adjacent host tissues and
allows discovery of CNC-dependent processes. Some groups have looked at bone deposition in controlling jaw
size, but our data suggest that bone resorption by mesodermally-derived osteoclasts with participation of CNC-
derived osteocytes control jaw size at later stages of development. We have previously shown that CNC controls
jaw size, bone resorption is controlled by CNC and that bone resorption controls jaw size. How CNC
accomplishes such a complex task, and what factors are sufficient to replicate this phenomenon, is unknown.
Likely candidates may include members and targets of WNT5A/ROR2 noncanonical signaling, since they are
known to play critical roles during bone resorption. Therefore, we hypothesize that by modulating WNT5A/ROR2
non-canonical signaling, CNC directs bone resorption to control jaw bone size. To test our hypothesis, we
propose two complementary and highly translational Specific Aims. Specific Aim 1 will determine the mechanism
by which CNC-derived osteocytes and mesodermally-derived osteoclasts act via WNT5A/ROR2 non-canonical
signaling to resorb bone and regulate jaw bone size. Specific Aim 2 will determine the mechanism via which
CNC acts by WNT5A/ROR2 noncanonical signaling to regulate the actions of osteoclast-mediated bone
resorption to regulate jaw bone size. We will employ gain- and loss-of-function techniques to identify molecular
mechanisms that endow CNC with the ability to control mandibular bone development. By determining the
precise mechanism of control of bone resorption by osteoclasts and osteocytes, future studies will be able to
develop accurate therapies to control lower jaw bone development.

## Key facts

- **NIH application ID:** 10491946
- **Project number:** 5R03DE031388-02
- **Recipient organization:** UNIVERSITY OF MISSOURI KANSAS CITY
- **Principal Investigator:** Erin Ealba Bumann
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $156,500
- **Award type:** 5
- **Project period:** 2021-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491946

## Citation

> US National Institutes of Health, RePORTER application 10491946, Wnt5a/Ror2 Signaling in Jaw Bone Development (5R03DE031388-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10491946. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*