Regulation of cell adhesion during embryonic compaction of mammalian embryos: Roles for PKC and beta-catenin

Beta-catenin has a number of roles in early development including involveme nt in cell adhesion, cell signaling, and developmental fate specification. This study investigates the mechanisms that regulate embryonic compaction, the first cell adhesion event in early mammalian development. Mammalian emb ryos can be induced to compact at an earlier developmental stage than norma l by treatment with agonists that activate protein kinase C (PKC), and this treatment is used to identify and analyze the minimum essential changes re quired for embryonic compaction. It was predicted that: (1) since activatio n of PKC can induce compaction prematurely in mouse embryos, phosphorylatio n of the protein components of the adherens complex would occur during indu ced compaction and that these components would be required for the cell adh esive event; (2) these same proteins should be phosphorylated during compac tion in normal development; (3) new, highly-specific inhibitors of PKC acti vity would inhibit compaction during normal development and induced compact ion; and (4) some PKC isotypes would become localized to the junctional mem branes during the process of compaction. In agreement with these prediction st, beta-catenin became phosphorylated on serine/threonine residues both du ring induced compaction and normal development. inhibitors to PKC, but not inhibitors to other kinases, blocked compaction. Furthermore, the alpha iso type of PKC is recruited to the membranes of the apposing blastomeres both during induced compaction and during normal development immediately before compaction begins and before beta-catenin becomes part of the detergent-res istant cytoskeleton at the junction. (C) 1999 Wiley-Liss, inc.