VARIANTS OF THE ALPHA(6)BETA(1)-LAMININ RECEPTOR IN EARLY MURINE DEVELOPMENT - DISTRIBUTION, MOLECULAR-CLONING AND CHROMOSOMAL LOCALIZATION OF 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 receptors that are members of the integrin family We have studied the expression of the alpha6 subunit of murine alpha6beta1 and its ligand, laminin, in preimplantation mouse embryos, embryo outgrowths and in embryonic stem (ES) cells and embryonal carcinoma (EC) cells. The alpha6 subunit is present in the oocyte and throughout preimplantation development. Laminin A chain appears later than alpha6 and has a more restricted distribution until the late blastocyst stage. Alpha6beta1 is strongly expressed in ES and EC cells; the levels of mRNA expression are not altered by differentiation. Molecular cloning of cDNA for the murine integrin alpha6 subunit from a mammary gland lambdagt11 library showed, as in man, an open reading frame encoding two variants Of alpha6, alpha6A and alpha6B. The identity of the alpha6 amino acid sequence to that in man and chicken is 93% and 73%, respectively. The gene for murine alpha6 was mapped to chromosome 2. While undifferentiated ES and EC cells express only alpha6B, alpha6A is co-expressed in ES cells after differentiation is induced by retinoic acid. Alpha6B is also the only variant expressed in blastocyst stage embryos, but when blastocysts have grown out in culture both alpha6A and alpha6B are expressed reflecting the results in the cell lines. We suggest that the deposition of laminin in the embryo is a receptor-mediated process and that the shift in the expression of the variants, as the inner cell mass forms its first differentiated progeny, reflects a change in functional properties.