Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic development is still unclear. Here we show that the main signalling centre orchestrating development of rodent incisors, the enamel knot (EK), is specified by a cell proliferation-driven buildup in compressive stresses (mechanical pressure) in the tissue. Direct mechanical measurements indicate that the stresses generated by cell proliferation are resisted by the surrounding tissue, creating a circular pattern of mechanical anisotropy with a region of high compressive stress at its centre that becomes the EK. Pharmacological inhibition of proliferation reduces stresses and suppresses EK formation, and application of external pressure in proliferation-inhibited conditions rescues the formation of the EK. Mechanical information is relayed intracellularly through YAP protein localization, which is cytoplasmic in the region of compressive stress that establishes the EK and nuclear in the stretched anisotropic cells that resist the pressure buildup around the EK. Together, our data identify a new role for proliferation-driven mechanical compression in the specification of a model signalling centre during mammalian organ development.

形态发生素的局部来源（称为信号传导中心）在器官发生过程中协调组织生长和细胞命运规范方面发挥着重要作用。然而，这些信号中心在胚胎发育过程中如何在组织中建立仍不清楚。在这里，我们表明，协调啮齿动物门牙发育的主要信号中心，牙釉质结（EK），是由细胞增殖驱动的组织中压应力（机械压力）的积累所指定的。直接机械测量表明，细胞增殖产生的应力受到周围组织的抵抗，形成机械各向异性的圆形图案，其中心有一个高压应力区域，即成为 EK。增殖的药理抑制可减少应激并抑制 EK 形成，在增殖抑制条件下施加外部压力可挽救 EK 的形成。机械信息通过 YAP 蛋白定位在细胞内传递，YAP 蛋白定位在压应力区域的细胞质中，建立 EK，而细胞核则位于拉伸的各向异性细胞中，抵抗 EK 周围的压力积聚。总之，我们的数据确定了增殖驱动的机械压缩在哺乳动物器官发育过程中模型信号中心规范中的新作用。