Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Functions of PRDM paralogs in craniofacial cartilage development

Award Number: R03DE036059
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/05/2026
PERIOD OF PERFORMANCE END DATE: 06/04/2028

Group Awards By:

View Award Description

Functions of PRDM paralogs in craniofacial cartilage development - Chondrocytes derived from cranial neural crest cells give rise to cartilaginous structures that form the craniofacial skeleton. These cells must undergo dynamic cellular processes of 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 among others. Our preliminary data suggest that in mice, two chromatin modifiers, PRDM3 and PRDM16, function together to facilitate development of craniofacial cartilage, specifically Meckel’s cartilage, which supports mandibular bone development. Combined loss of both Prdm3 and Prdm16 using the Wnt1-Cre driver leads to a complete absence of the Meckel’s cartilage, likely due to misregulation of Wnt/β-catenin transcriptional activity. The specificity of this phenotype varies with the alleles lost as combinatorial mutants exhibit varying phenotypic severity. The goal of this proposal is to further define the mechanisms by which these two PRDM paralogs function to facilitate craniofacial cartilage development. The aims outlined in this proposal will utilize a combination of genetic mouse models with in vitro cell culture systems and molecular tools to test the hypothesis that precise levels of PRDM3 and PRDM16 fine-tune activation and repression of canonical Wnt/β-catenin transcriptional activity and its downstream GRN to control chondrocyte differentiation. In Aim 1, the molecular mechanisms controlling chondrocyte differentiation through Wnt/β-catenin transcriptional activity in the developing murine mandibular process will be defined across the Prdm3;Prdm16 combinatorial mutant allelic series through comprehensive histological assessments over developmental time. Additionally, a thorough evaluation of global transcriptomic changes will be performed, and direct gene targets will be identified through CUT&RUN experiments. Aim 2 will determine if precise modulation of PRDM protein levels refine Wnt/β-catenin activity and contributes to the dosage-dependent craniofacial chondrocyte phenotypes observed in mice. We will develop and apply the degradation tag (dTAG/BromoTag) systems to precisely control PRDM protein dosage in an in vitro model of cranial neural crest development. Together, the results from these studies will provide the tools and concepts to further explore these mechanisms in an R01 application. 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $305,000 )
2026	2026	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	1	6/5/2026	NEW	$305,000
														Subtotal = $305,000

Grand Total All Awards = $305,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Functions of PRDM paralogs in craniofacial cartilage development

Award Number: R03DE036059

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/05/2026

PERIOD OF PERFORMANCE END DATE: 06/04/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer