# Tracing the origins of craniofacial growth plates

> **NIH NIH R03** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $159,000

## Abstract

PROJECT SUMMARY
Growth of the skeleton occurs at specialized sites called growth plates and sutures. Where these growth
sites are located and how long they persist postnatally determine the final shape and size of the skeleton.
The prevalence of skeletal dysplasias affecting bone or cartilage growth in humans (estimated to impact
approximately one in 4,000-5,000 births) has motivated a vast body of research into the pathways regulating
growth plate and suture development and function. However, the field still lacks a basic understanding of
the mechanisms that determine where these critical sites form within the skeleton. Growth plates in particular
have been typically assumed to form passively between centers of endochondral ossification. However, a
scattering of cell polarity data from zebrafish, mice, and chick indicate that growth plates may be prefigured
in the cartilage template well before ossification begins, suggesting an active patterning process. This
application presents a novel hypothesis for growth plate origins, to be tested in zebrafish using an innovative
fate-mapping strategy newly applied to the skeletal system.
Growth plates are present in endochondral bones of the craniofacial skeleton as well as the long bones of
the limbs. Prior to the onset of bone or cartilage differentiation in the head, skeletal progenitors for the face
express distinct cohorts of genes depending on their position on the dorsal-ventral (DV) axis. These domains
are not entirely mutually exclusive: a line of cells co-expressing markers characteristic of the neighboring
domains can typically be detected at each boundary. Importantly, the positions of these boundaries appear
to correlate with the eventual distribution of growth plates and cartilaginous joints in the adult skull. This
observation prompted the hypothesis that cartilaginous growth zones in the skull are destined to form at
these molecular boundaries. Testing this hypothesis requires following the fate of embryonic boundary cells
to adulthood. To this end, an underutilized but powerful intersectional split-Intein-Cre lineage-tracing method
will be used to specifically label cells co-expressing markers of adjacent DV domains. The pilot study
outlined here will provide the first test of this original hypothesis, validate the methodology, and create
reagents for future extensions of this work, all prerequisites for future R01-level support.
This proposal directly aligns with the NIDCR's call to investigate mechanisms of development, maintenance,
and remodeling of craniofacial tissues. Though the scope is currently limited to the skull, the principles under
study may also apply to many other parts of the endochondral skeleton and possibly also to cranial sutures.
Results from this work could stimulate a major advance in understanding the logic governing skeletal
patterning, with clear relevance for human craniofacial malformations and other skeletal dysplasias.

## Key facts

- **NIH application ID:** 10413816
- **Project number:** 5R03DE030200-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Lindsey Anne Barske
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $159,000
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413816

## Citation

> US National Institutes of Health, RePORTER application 10413816, Tracing the origins of craniofacial growth plates (5R03DE030200-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10413816. Licensed CC0.

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