Mammalian teeth,developing inseparable from epithelial-mesenchymal interaction,come in many shapes and the key factors governing tooth morphology deserve to be answered.By merging single-cell RNA sequencing analysis with lineage tracing models,we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+cells within M1.These PRX1+cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation.Deeper into the mechanisms,we have discovered that Wnt5a,bestowed by mesenchymal PRX1+cells,stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway.The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1.Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs.These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
Gene Expression Regulation, Developmental ; Odontogenesis ; Signal Transduction ; Tooth/metabolism* ; Humans

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1⁺ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1⁺ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1⁺ cells in PDL cells. The behavior of PRX1⁺ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1⁺ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1⁺ cells; during transplanted teeth PDL reconstruction, PRX1⁺ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1⁺ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.
Animals ; Cell Differentiation ; Mesenchymal Stem Cells ; Mice ; Molar ; Osteogenesis/physiology* ; Periodontal Ligament