The article reviews the role of the extracellular matrix (ECM) in controlling cell differentiation and the signaling mechanisms through which ECM proteins interact with cells via integrin receptors. Integrins, a family of heterodimeric cell surface receptors, mediate the adhesive interactions between cells and the ECM, which play crucial roles in embryonic development and adult tissue homeostasis. The article highlights several examples of how cell differentiation and gene expression are regulated by adhesive interactions with the ECM, such as the induction of c-fos and pro α(I) collagen expression in fibroblasts and the activation of metalloprotease genes in fibroblastic cells. The signaling pathways initiated by integrin-mediated adhesion involve the activation of tyrosine kinases, particularly pp125 Focal Adhesion Kinase (pp125FAK), which can lead to changes in gene expression. The article also discusses the specificity of gene induction in monocytes, where different ECM components result in distinct patterns of gene expression. The relationship between integrin-mediated signaling and growth factor receptor signaling pathways is explored, suggesting potential intersections and parallels in their mechanisms. Finally, the article outlines several unresolved issues, including the precise mechanisms of integrin-pp125FAK interaction and the downstream events following integrin clustering or cell adhesion.The article reviews the role of the extracellular matrix (ECM) in controlling cell differentiation and the signaling mechanisms through which ECM proteins interact with cells via integrin receptors. Integrins, a family of heterodimeric cell surface receptors, mediate the adhesive interactions between cells and the ECM, which play crucial roles in embryonic development and adult tissue homeostasis. The article highlights several examples of how cell differentiation and gene expression are regulated by adhesive interactions with the ECM, such as the induction of c-fos and pro α(I) collagen expression in fibroblasts and the activation of metalloprotease genes in fibroblastic cells. The signaling pathways initiated by integrin-mediated adhesion involve the activation of tyrosine kinases, particularly pp125 Focal Adhesion Kinase (pp125FAK), which can lead to changes in gene expression. The article also discusses the specificity of gene induction in monocytes, where different ECM components result in distinct patterns of gene expression. The relationship between integrin-mediated signaling and growth factor receptor signaling pathways is explored, suggesting potential intersections and parallels in their mechanisms. Finally, the article outlines several unresolved issues, including the precise mechanisms of integrin-pp125FAK interaction and the downstream events following integrin clustering or cell adhesion.