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Free keywords:
FOCAL ADHESION KINASE; STEM-CELLS; BASEMENT-MEMBRANES; PAR PROTEINS;
POLARITY; MECHANISMS; EXPRESSION; EPIBLAST; FAILURE; LAMININCell Biology;
Abstract:
At implantation, the embryo establishes contacts with the maternal endometrium. This stage is associated with a high incidence of preclinical pregnancy losses. While the maternal factors underlying uterine receptivity have been investigated, the signals required by the embryo for successful peri-implantation development remain elusive. To explore these, we studied integrin beta 1 signaling, as embryos deficient for this receptor degenerate at implantation. We demonstrate that the coordinated action of pro-survival signals and localized actomyosin suppression via integrin beta 1 permits the development of the embryo beyond implantation. Failure of either process leads to developmental arrest and apoptosis. Pharmacological stimulation through fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1), coupled with ROCK-mediated actomyosin inhibition, rescues the deficiency of integrin beta 1, promoting progression to post-implantation stages. Mutual exclusion between integrin beta 1 and actomyosin seems to be conserved in the human embryo, suggesting the possibility that these mechanisms could also underlie the transition of the human epiblast from pre- to post-implantation.
