COMPLEX PATTERNS OF EXPRESSION SUGGEST EXTENSIVE ROLES FOR THE ALPHA(2)BETA(1) INTEGRIN IN MURINE DEVELOPMENT

The extracellular matrix plays important roles in embryogenesis. The integrin family of adhesion receptors may mediate critical cellular interactions with the extracellular matrix during development. In this study, we elucidated the developmental spatial and temporal expression pattern of the alpha(2) beta(1) integrin heterodimer, a cell surface receptor for collagens and laminin. We generated reagents for studying the a,P, integrin and examined the developmental expression of the integrin in postimplantation mice. A partial length murine alpha(2) cDNA was isolated and the protein encoding region was found to be 82% homologous to that of the human alpha(2) cDNA. A synthetic peptide corresponding to the carboxy-terminus of murine alpha(2) was used to generate alpha(2)-specific antiserum. The antiserum and riboprobes derived from both the alpha(2) cDNA and the previously characterized murine beta(1) subunit cDNA were used to determine the spatiotemporal expression of the alpha(2) subunit by immunocytochemistry and of the alpha(2) and beta(1) mRNAs by in situ hybridization. Both approaches gave concordant results. Expression of the alpha(2) integrin subunit was observed in both the maternal and embryonic components of the placenta, namely the perivascular and basal zone decidual cells and decidual cells and spongiotrophoblasts at the maternal/embryonic junction. Expression was also observed in cells actively producing and remodeling the extracellular matrix in the maternal uterus and in the developing gut, lens, cartilage, bone, and tooth of the embryo. Generally, expression of the alpha(2), integrin subunit was found in cells entering their later stages of differentiation such as in chondrocytes as they became hypertrophic, ameloblasts and odontoblasts as they became columnar and began to secrete the matrix of the tooth, endothelial cells after they formed tubules, in the lens just prior to and during lens fiber production, and in the collecting ducts of the kidney only after full gestation. Throughout embryogenesis, beta(1) mRNA was widely distributed and present in cell types expressing beta(1) mRNA and protein. The developmental expression pattern of the alpha(2) beta(1) integrin suggests roles for the integrin in placental development and matrix assembly and remodeling. (C) 1994 Wiley-Liss, Inc.