The article discusses the critical role of the microenvironment in regulating cell behavior, particularly in the context of tissue architecture, development, homeostasis, and cancer. The authors emphasize that the behavior of cells is largely determined by their interactions with the extracellular matrix (ECM), neighboring cells, and soluble cues. They introduce the concept of "dynamic reciprocity," which describes how the ECM and its receptors interact with the cytoskeleton and nuclear matrix to modulate gene expression and cell differentiation. The article highlights the importance of tissue-specific interactions, such as those between epithelial and mesenchymal cells, in directing tissue development and function. It also explores how the microenvironment can influence the response to oncogenic insults, including mutations, and how this context-dependent signaling can lead to the reversion of a malignant phenotype to a normal one. The authors argue that tissue architecture is both a consequence and a cause of development, and that it plays a crucial role in maintaining homeostasis and preventing cancer. They conclude by emphasizing the need for an interdisciplinary approach to understand the complex language of tissue architecture and signaling.The article discusses the critical role of the microenvironment in regulating cell behavior, particularly in the context of tissue architecture, development, homeostasis, and cancer. The authors emphasize that the behavior of cells is largely determined by their interactions with the extracellular matrix (ECM), neighboring cells, and soluble cues. They introduce the concept of "dynamic reciprocity," which describes how the ECM and its receptors interact with the cytoskeleton and nuclear matrix to modulate gene expression and cell differentiation. The article highlights the importance of tissue-specific interactions, such as those between epithelial and mesenchymal cells, in directing tissue development and function. It also explores how the microenvironment can influence the response to oncogenic insults, including mutations, and how this context-dependent signaling can lead to the reversion of a malignant phenotype to a normal one. The authors argue that tissue architecture is both a consequence and a cause of development, and that it plays a crucial role in maintaining homeostasis and preventing cancer. They conclude by emphasizing the need for an interdisciplinary approach to understand the complex language of tissue architecture and signaling.