Understanding human organ formation is a scientific challenge with far-reaching medical implications^1,2. Three-dimensional stem-cell cultures have provided insights into human cell differentiation^3,4. However, current approaches use scaffold-free stem-cell aggregates, which develop non-reproducible tissue shapes and variable cell-fate patterns. This limits their capacity to recapitulate organ formation. Here we present a chip-based culture system that enables self-organization of micropatterned stem cells into precise three-dimensional cell-fate patterns and organ shapes. We use this system to recreate neural tube folding from human stem cells in a dish. Upon neural induction^5,6, neural ectoderm folds into a millimetre-long neural tube covered with non-neural ectoderm. Folding occurs at 90% fidelity, and anatomically resembles the developing human neural tube. We find that neural and non-neural ectoderm are necessary and sufficient for folding morphogenesis. We identify two mechanisms drive folding: (1) apical contraction of neural ectoderm, and (2) basal adhesion mediated via extracellular matrix synthesis by non-neural ectoderm. Targeting these two mechanisms using drugs leads to morphological defects similar to neural tube defects. Finally, we show that neural tissue width determines neural tube shape, suggesting that morphology along the anterior–posterior axis depends on neural ectoderm geometry in addition to molecular gradients⁷. Our approach provides a new route to the study of human organ morphogenesis in health and disease.

了解人体器官的形成是一项具有深远医学意义的科学挑战^1,2。三维干细胞培养提供了对人类细胞分化的见解^3,4。然而，目前的方法使用无支架的干细胞聚集体，它会形成不可复制的组织形状和可变的细胞命运模式。这限制了他们概括器官形成的能力。在这里，我们展示了一种基于芯片的培养系统，该系统能够将微图案化干细胞自组织成精确的三维细胞命运模式和器官形状。我们使用该系统从培养皿中的人类干细胞中重建神经管折叠。神经诱导后^5,6，神经外胚层折叠成一个毫米长的神经管，上面覆盖着非神经外胚层。折叠以 90% 的保真度发生，在解剖学上类似于发育中的人类神经管。我们发现神经和非神经外胚层对于折叠形态发生是必要且充分的。我们确定了两种驱动折叠的机制：(1) 神经外胚层的顶端收缩，和 (2) 非神经外胚层通过细胞外基质合成介导的基底粘附。使用药物针对这两种机制会导致类似于神经管缺陷的形态学缺陷。最后，我们表明神经组织宽度决定了神经管的形状，这表明除了分子梯度之外，沿着前后轴的形态还取决于神经外胚层的几何形状⁷. 我们的方法为研究健康和疾病中的人体器官形态发生提供了一条新途径。