The a6pl integrin is a receptor for laminins and is present from early stages of mouse embryogenesis. In the present study we determined the temporal and spatial expression of the two cytoplasmic splice variants of the a6 integrin subunit, a6A and a6B, in the early-and midgestation mouse postimplantation embryo using RT-PCR, in situ hybridization, and immunofluorescence. Our results show that a6B is present in the embryo at all stages studied and is expressed before a6A. a6A expression begins in 8.5 day p.c. embryos and is initially exclusively localized to the developing heart. In 8.5 (and 9.5) day p.c. embryos a6A mRNA and protein are present in a gradient in the myocardium of the heart tube from strongest expression in the sinus venosus and in the common atrial chamber to a weakening expression along the ventricle and bulbus cordis. In 10.5 day p.c. embryos this gradient is less evident and in 12.5 day p.c. embryos a6A mRNA and protein are present in comparable amounts between atria and ventricles. Neither a6A nor a6B is present in endocardial cushion tissue. By day 12.5 p.c. (w6A expression is also present in the developing epidermis, dental primordia, lens, gonads, and in a few epithelia such as those of the digestive tract. a6B expression is always much more widespread than a6A expression. For example, only a6B is present in the myotome of the somites of 9.5 day p.c, embryos, in the developing central and peripheral nervous systems, and in the nephrogenic system at all stages studied, except after the differentiation of the gonads when a6A is also present. Furthermore, a6B is the only splice variant present on endothelial cells. We also examined the distribution of the f34 integrin subunit to determine whether the a6P4 integrin was present during these stages of development. p4 protein was absent in early postimplantation stages but was present in the epidermis and digestive tract of 12.5 day p.c. embryos. These results show a differential distribution of a6A and a6B during mouse development and thus strongly suggest a different function of these splice variants during embryogenesis. Our results point to a possible role for the 0 1995 WILEY-LISS, INC. a6Apl integrin in the development of the myocardium of the developing heart, but not in the migration of endocardial cushion cells, while a6Bp1 could be important in the developing nephrogenic and nervous systems. o l W 5 Wiley-Liss, Inc.