PRDM paralogs are required for Meckel's cartilage formation during mandibular bone development
Qootsvenma Denipah-Cook1, Bryanna V Saxton1, Kristin B Artinger2
1Department of Biology, University of New Mexico, Albuquerque, NM, USA.
Biorxiv : the Preprint Server for Biology
|August 8, 2025
Summary
Histone methyltransferases PRDM3 and PRDM16 are crucial for neural crest cell differentiation into chondrocytes, ensuring proper mandibular bone development and Meckel's cartilage formation. Their absence disrupts Wnt/β-catenin signaling, leading to craniofacial abnormalities.
Area of Science:
- Developmental Biology
- Craniofacial Development
- Epigenetics
Background:
- Mandibular bone development involves both endochondral and intramembranous ossification, originating from neural crest cells (NCCs).
- Wnt/β-catenin signaling critically regulates osteogenic versus chondrogenic differentiation of osteochondroprogenitors.
- Chromatin remodelers play a hierarchical role in controlling gene regulatory networks during development.
Purpose of the Study:
- To investigate the function of histone methyltransferases PRDM3 and PRDM16 in murine craniofacial development.
- To understand the role of PRDM3 and PRDM16 in regulating NCC differentiation and Meckel's cartilage formation.
Main Methods:
- Conditional ablation of Prdm3 and Prdm16 in NCC lineage using Wnt1-Cre driver in mice.
- Histological analysis of craniofacial development at embryonic day 18.5 (E18.5).
- Assessment of cell proliferation (phosphoH3+) and apoptosis (cleaved caspase3+).
- Analysis of mRNA transcripts and protein abundance of Wnt/β-catenin signaling components.
Main Results:
- Ablation of Prdm3 and Prdm16 resulted in severe mandibular hypoplasia and absence of Meckel's cartilage.
- Increased osteoblast precursors (RUNX2+) and decreased chondrogenic cells (SOX9+) were observed, indicating a shift in cell fate.
- No significant changes in proliferation or apoptosis suggested a defect in NCC fate determination.
- Elevated Wnt/β-catenin signaling components were detected, implying PRDM3 and PRDM16 normally restrict this pathway to promote chondrogenesis.
Conclusions:
- PRDM3 and PRDM16 are essential for NCC differentiation towards chondrocytes during Meckel's cartilage formation.
- These chromatin remodelers control Wnt/β-catenin signaling activity, ensuring proper chondrogenesis and mandibular morphogenesis.
- Dysregulation of PRDM3/PRDM16 impacts NCC fate decisions, leading to craniofacial abnormalities.
