Expression patterns of laminin receptor splice variants α6Aβ1 and α6Bβ1 suggest different roles in mouse development

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Abstract
The α6β1 integrin is a receptor for laminins and is present from early stages of mouse embryogenesis. In the present study determined the temporal and spatial expression of the two cytoplasmic splice variants of the α6 integrin subunit, α6A and α6B, in the early‐ and midgestation mouse postimplantation embryo using RT‐PCR, in situ hybridization, and immunofluorescence. Our results show that α6B is present in the embryo at all stages studied and is expressed before α6A. α6A 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 α6A 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 α6A mRNA and protein are present in comparable amounts between atria and ventricles. Neither α6A nor α6B is present in endocardial cushion tissue. By day 12.5 p.c. α6A expression is also present in the developing epidermis, dental primordia, lens, gonads, and in a few epithelia such as those of the digestive tract. α6B expression is always much more widespread than α6A expression. For example, only α6B 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 α6A is also present. Furthermore, α6B is the only splice variant present on endothelial cells. We also examined the distribution of the β4 integrin subunit to determine whether the α6β4 integrin was present during these stages of development. β4 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 α6A and α6B 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 α6Aβ1 integrin in the development of the myocardium of the developing heart, but not in the migration of endocardial cushion cells, while α6Bβ1 could be important in the developing nephrogenic and nervous systems.