PRX1-positive mesenchymal stem cells drive molar morphogenesis.

Area of Science:

• Developmental Biology
• Genetics
• Cell Biology

Background:

• Tooth morphology is complex and influenced by epithelial-mesenchymal interactions.
• Understanding the factors controlling tooth shape is a key question in mammalian development.

Purpose of the Study:

• To investigate the role of specific cell populations in determining mouse molar morphology.
• To elucidate the molecular mechanisms underlying tooth shape determination.

Main Methods:

• Single-cell RNA sequencing analysis.
• Lineage tracing models in mice.
• Analysis of Wnt5a signaling pathway activation.

Main Results:

• A correlation was found between PRX1-positive cells in M1 and contrasting molar morphology.
• PRX1-positive cells regulate dental mesenchymal cell proliferation.
• Wnt5a, secreted by PRX1-positive cells, drives mesenchymal proliferation and molar morphogenesis via WNT signaling.
• Wnt5a deficiency phenocopies Prx1 deficiency, and WNT5A addition rescues Prx1-deficient tooth germ defects.

Conclusions:

• PRX1-positive mesenchymal cells are critical regulators of tooth morphology.
• The Wnt5a signaling pathway mediated by PRX1-positive cells is essential for normal molar development.
• PRX1-positive mesenchymal cells represent a potential therapeutic target for regulating tooth morphology.