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 i ntegrin family of adhesion receptors may mediate critical cellular int eractions with the extracellular matrix during development. In this st udy, we elucidated the developmental spatial and temporal expression p attern of the alpha(2) beta(1) integrin heterodimer, a cell surface re ceptor for collagens and laminin. We generated reagents for studying t he a,P, integrin and examined the developmental expression of the inte grin in postimplantation mice. A partial length murine alpha(2) cDNA w as isolated and the protein encoding region was found to be 82% homolo gous to that of the human alpha(2) cDNA. A synthetic peptide correspon ding to the carboxy-terminus of murine alpha(2) was used to generate a lpha(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 be ta(1) mRNAs by in situ hybridization. Both approaches gave concordant results. Expression of the alpha(2) integrin subunit was observed in b oth the maternal and embryonic components of the placenta, namely the perivascular and basal zone decidual cells and decidual cells and spon giotrophoblasts at the maternal/embryonic junction. Expression was als o observed in cells actively producing and remodeling the extracellula r matrix in the maternal uterus and in the developing gut, lens, carti lage, bone, and tooth of the embryo. Generally, expression of the alph a(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 se crete the matrix of the tooth, endothelial cells after they formed tub ules, in the lens just prior to and during lens fiber production, and in the collecting ducts of the kidney only after full gestation. Throu ghout embryogenesis, beta(1) mRNA was widely distributed and present i n cell types expressing beta(1) mRNA and protein. The developmental ex pression pattern of the alpha(2) beta(1) integrin suggests roles for t he integrin in placental development and matrix assembly and remodelin g. (C) 1994 Wiley-Liss, Inc.