VARIANTS OF THE ALPHA(6)BETA(1)-LAMININ RECEPTOR IN EARLY MURINE DEVELOPMENT - DISTRIBUTION, MOLECULAR-CLONING AND CHROMOSOMAL LOCALIZATIONOF THE MOUSE INTEGRIN ALPHA(6)-SUBUNIT

Laminin (A:B1:B2) is a major component of the first basement membrane to appear in the developing mouse embryo. Its effects on morphogenesis and differentiation are mediated by interaction with cell surface rec eptors that are members of the integrin family We have studied the exp ression of the alpha6 subunit of murine alpha6beta1 and its ligand, la minin, in preimplantation mouse embryos, embryo outgrowths and in embr yonic stem (ES) cells and embryonal carcinoma (EC) cells. The alpha6 s ubunit is present in the oocyte and throughout preimplantation develop ment. Laminin A chain appears later than alpha6 and has a more restric ted distribution until the late blastocyst stage. Alpha6beta1 is stron gly expressed in ES and EC cells; the levels of mRNA expression are no t altered by differentiation. Molecular cloning of cDNA for the murine integrin alpha6 subunit from a mammary gland lambdagt11 library showe d, as in man, an open reading frame encoding two variants Of alpha6, a lpha6A and alpha6B. The identity of the alpha6 amino acid sequence to that in man and chicken is 93% and 73%, respectively. The gene for mur ine alpha6 was mapped to chromosome 2. While undifferentiated ES and E C cells express only alpha6B, alpha6A is co-expressed in ES cells afte r differentiation is induced by retinoic acid. Alpha6B is also the onl y variant expressed in blastocyst stage embryos, but when blastocysts have grown out in culture both alpha6A and alpha6B are expressed refle cting the results in the cell lines. We suggest that the deposition of laminin in the embryo is a receptor-mediated process and that the shi ft in the expression of the variants, as the inner cell mass forms its first differentiated progeny, reflects a change in functional propert ies.