Preimplantation development in the mouse culminates in the production of a fluid-filled blastocyst comprised of two cell lineages: the first differentiated epithelium, the trophectoderm, and the inner cell mass. Proper functioning of the trophectoderm during attachment to and penetration of maternal uterine tissue is critical to the survival of the embryo. The process of epithelialization which leads to the formation of the trophectoderm lineage is poorly understood. However, cell-cell adhesion molecules and molecules that are restricted to a particular membrane domain on cleavage stage embryos are candidates for being critically involved in that process. Using immunohistochemical and biochemical techniques, and specific antibodies, we will study the expression of cell-cell adhesion molecules [cell CAM 120/80 (identified by this group, galactosyltransferase, desmosome-associated glycoprotein II] during preimplantation development. These studies will document the onset of the expression of these molecules during early cleavage and will reveal any changes in their distributions that occur during compaction and polarization of the 8 cell embryo, and during junction formation and blastulation. Antibodies against the apical, trophectoderm-specific BL antigens (identified by this group), will be used to study their re-expression on inner cell mass cells as a result of experimental decompaction of morulae and inner cell masses. These studies should enhance our understanding of the molecular basis of early morphogenetic events associated with blastulation and trophectoderm lineage segregation. Once the mouse blastocyst has hatched, it must attach successfully to the uterine epithelium and penetrate the underlying basal lamina and uterine stroma. Therefore, the blastocyst must express receptors for molecules in extracellular matrices and for molecules on the uterine epithelium. Previous studies from this group have shown that an antibody against a group of 140 kd glycoproteins inhibits blastocyst attachment to laminin and fibronectin. We will use specific antibodies against surface glycoconjugates known to be involved in cell matrix adhesion in cultured cells (fibronectin and laminin receptors, cell surface heparan sulfate proteoglycan) to study their expression in preimplantation mouse embryos. Both immunohistochemical and biochemical approaches will be used. Molecules on the surface of the blastocyst and the uterine epithelium involved in their initial interaction are unknown. Using an in vitro culture model, in which uterine epithelium is grown on a basal lamina/collagen gel substrate, and heterospecific antisera against uterine cell surface material and against hatched blastocysts, we will attempt to inhibit the interaction of the blastocyst and uterine epithelium and then to identify the relevant molecules. Taken together, all of these studies should increase greatly, our knowledge of the molecular basis for the adhesive processes essential for promoting successful blastulation and implantation.
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| Sutherland, A E; Calarco, P G; Damsky, C H (1988) Expression and function of cell surface extracellular matrix receptors in mouse blastocyst attachment and outgrowth. J Cell Biol 106:1331-48 |
