Implantation in humans and mice is dependent on the ability of trophoblast cells to modify their phenotype from a transporting to an invasive epithelium. Trophoblast invasion begins with the adhesion of the exterior blastocyst surface to the basal lamina underlying luminal epithelial cells. Acquisition of this invasive phenotype is accompanied by translocation of the a5b1 integrin complex to the apical plasma membrane of trophoblast. Strong binding to the extracellular matrix protein, fibronectin, requires contact with fibronectin and protein trafficking. It is of interest to delineate the signal transduction cascade involved in this important developmental event. A large number of proteins have been identified that interact with integrins to mediate signal transduction and regulate their ligand binding activity. Treatment of morula-stage embryos with inhibitors of RNA synthesis inhibit expression of fibronectin-binding activity. Furthermore, acquisition of fibronectin-binding activity does not appear to involve increases in the cell surface expression of various integrins on blastocysts. Therefore, it is hypothesized that some genes transcribed during this critical morula-blastocyst transition mediate enhanced fibronectin-binding activity. Differential display will be used to identify genes first expressed at cavitation. These amplicons will be isolated and sequenced and compared to sequences in available databases. Highest priority will be given to the further study of known genes that could interact with integrins. Based on previous studies from the PI's lab, it is anticipated that such genes will be associated with intracellular calcium signaling, tyrosine phosphorylation or protein trafficking.
| Martínez-Hernández, M G; Baiza-Gutman, L A; Castillo-Trápala, A et al. (2011) Regulation of proteinases during mouse peri-implantation development: urokinase-type plasminogen activator expression and cross talk with matrix metalloproteinase 9. Reproduction 141:227-39 |
| Wang, Jun; Mayernik, Linda; Armant, D Randall (2007) Trophoblast adhesion of the peri-implantation mouse blastocyst is regulated by integrin signaling that targets phospholipase C. Dev Biol 302:143-53 |
| Armant, D Randall (2005) Blastocysts don't go it alone. Extrinsic signals fine-tune the intrinsic developmental program of trophoblast cells. Dev Biol 280:260-80 |
