形态发生素是局部产生的信号分子，形成浓度梯度来引导组织图案化。组织模式是形态发生素扩散和响应细胞行为之间的协作而出现的，但扩散形态发生素在生物波动中定义精确空间模式的机制仍不清楚。为了研究细胞如何响应扩散蛋白以生成组织模式，我们开发了 SYMPLE3D，一个 3D 培养平台。通过设计对人工形态发生素响应的基因表达，我们观察到将形态发生素信号与基于钙粘蛋白的粘附耦合足以将形态发生素梯度转化为不同的组织域。形态原诱导的钙粘蛋白将激活的细胞聚集到单个域中，去除异位激活的细胞。此外，我们揭示了钙粘蛋白介导的压缩和细胞混合的类似开关诱导，使形态发生素梯度内的激活细胞均质化，形成具有清晰边界的均匀激活域。这些发现强调了形态发生素梯度和细胞粘附在稳健组织图案化中的合作，并引入了一种组织工程开发类器官新组织域的新方法。© 2024。作者。

Morphogens, locally produced signaling molecules, form a concentration gradient to guide tissue patterning. Tissue patterns emerge as a collaboration between morphogen diffusion and responsive cell behaviors, but the mechanisms through which diffusing morphogens define precise spatial patterns amidst biological fluctuations remain unclear. To investigate how cells respond to diffusing proteins to generate tissue patterns, we develop SYMPLE3D, a 3D culture platform. By engineering gene expression responsive to artificial morphogens, we observe that coupling morphogen signals with cadherin-based adhesion is sufficient to convert a morphogen gradient into distinct tissue domains. Morphogen-induced cadherins gather activated cells into a single domain, removing ectopically activated cells. In addition, we reveal a switch-like induction of cadherin-mediated compaction and cell mixing, homogenizing activated cells within the morphogen gradient to form a uniformly activated domain with a sharp boundary. These findings highlight the cooperation between morphogen gradients and cell adhesion in robust tissue patterning and introduce a novel method for tissue engineering to develop new tissue domains in organoids.© 2024. The Author(s).