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.

哺乳动物牙齿的发育与上皮间质相互作用密不可分，具有多种形状，控制牙齿形态的关键因素值得解答。通过将单细胞 RNA 测序分析与谱系追踪模型相结合，我们发现了小鼠磨牙的对比形态与 M1 内 PRX1 ⁺细胞的特定存在之间的迷人相关性。这些 PRX1 ⁺细胞通过牙齿间充质细胞增殖的显着差异，在塑造牙齿形态方面承担着重要的责任。更深入地研究机制，我们发现间充质 PRX1 ⁺细胞赋予的Wnt5a刺激间充质细胞增殖，同时通过 WNT 信号通路协调摩尔形态发生。 Wnt5a的缺失表现出与 siPrx1 相似的缺陷表型。外源添加 WNT5A 可以成功逆转Prx1缺陷牙胚中受抑制的细胞增殖和随之而来的异常外观。这些发现提供了令人信服的证据，证明 PRX1 阳性间充质细胞是调节牙齿形态的潜在目标。