# Functions of PRDM Histone Methyltransferases during Cartilage Development in the Craniofacial Skeleton

> **NIH NIH K99** · UNIVERSITY OF COLORADO DENVER · 2022 · $100,000

## Abstract

Chondrocytes derived from cranial neural crest cells give rise to cartilaginous structures that form the craniofacial
skeleton. These cells must undergo numerous cellular processes including condensation, orientation,
intercalation, proliferation, differentiation, and maturation before forming a template that will serve as a scaffold
for subsequent bone formation. The gene regulatory networks (GRNs) and signaling pathways, controlling these
processes need to be tightly regulated. Any alteration to the GRNs or signaling modules during chondrocyte
maturation and differentiation can compromise the skeletal integrity of the developing craniofacial tissues and
contribute to the etiology of congenital defects including but not limited to cleft lip with or without cleft palate,
mandibular hypoplasia, craniosynostosis. I am interested in understanding how the chromatin modifiers, Prdm3
and Prdm16, epigenetically control spatial and temporal gene expression during craniofacial development. The
aims outlined in this proposal utilize molecular, genetic and epigenetic tools in both zebrafish and mice to test
the hypothesis that Prdm3 and Prdm16 act upstream of Wn/β-catenin to properly balance chondrocyte
functionality during the formation of the craniofacial complex. In Aim 1, the molecular mechanisms controlling
Wnt/β-catenin transcriptional activity in chondrocytes during zebrafish craniofacial development will be defined.
The conserved functions of chondrocyte polarity and differentiation through regulation of Wnt/β-catenin will be
identified in the mammalian craniofacial complex (Aim 2), and lastly, the functions of conserved Prdm3- and
Prdm16-regulated canonical Wnt/β-catenin enhancers across vertebrates in the craniofacial mesenchyme will
be assessed (Aim 3). Completion of these aims will provide insight on how these epigenetic modifiers control
specific GRNs and signaling modules (Wnt/β-catenin) to facilitate proper chondrogenesis in formation of the
craniofacial skeleton. Importantly, this project will also provide mechanistic insight behind how loss of these
factors contributes to the development of craniofacial disorders. The research training plan along with the career
development and mentorship plan outlined in this proposal are designed to provide the foundation for my career
goal of becoming an independent investigator at a top research institution. During the K99 phase, I will receive
mentorship in zebrafish biology from Kristin Artinger, as well as guidance from members on my advisory
committee for mouse craniofacial biology and bioinformatics analysis. An extensive career development plan
with activities promoting grant writing, scientific communication, and leadership and mentoring skills, in alignment
with the MOSAIC program, will facilitate my transition to an independent faculty position during the R00 phase.
The Craniofacial Department at the University of Colorado Anschutz Medical Campus offers an exceptional
environment with countless...

## Key facts

- **NIH application ID:** 10349685
- **Project number:** 1K99DE031349-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Lomeli Carpio Shull
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349685

## Citation

> US National Institutes of Health, RePORTER application 10349685, Functions of PRDM Histone Methyltransferases during Cartilage Development in the Craniofacial Skeleton (1K99DE031349-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10349685. Licensed CC0.

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