Role of signalling of the pre- to post-implantation development in the mouse embryo

Objective: At implantation, the embryo undergoes a critical transformation process which requires precise spatiotemporal control of key signalling pathways, important for morphogenesis and cell fate specification. The aim of this study is to use an in vitro approach permitting to investigate how the morphogenetic organization of the embryo become established during the transition of pre- to post-implantation which cannot be traced inside of the maternal tissue in vivo. Method: In this study, by using a protocol permitting the embryo development beyond implantation stage in vitro, the role of BMP/Smad-p38MAPK signalling events during this pre-to-postimplantation transition was investigated first time in the literature. In addition, we investigated the morphogenetic events of tissue remodelling during pre- to post-implantation transition by recapitulating the tissue formation and generating the embryo-like structures from the embryonic and trophoblast stem cells. Live imaging after using RNAi technology and molecular inhibitor applications were used, and, numerous tissue-specific molecular markers have been extensively explored with qRT-PCR and confocal microscopy analyses. Results: It has been determined that the inhibition of Smad1/5/8 decreases expression of key molecular elements such as Eomes and Elf5, thereby endangering ExE tissue continuity and decreasing proliferation. Smad-dependent BMP signaling inhibition has also been shown to induce premature pluripotency phase change by increasing expression of Acsl4, Dll3, Fgf5, Otx2 in epiblast and embryonic stem cells, and, therefore, inducing cell death. Conclusion: As a result, Smad-dependent BMP signaling mechanisms have been observed to play a direct role in the maintanence of extraembryonic tissue and stem cells during pre-to-post implantation transition. Molecular defects which occured as a result of BMP/Smad inhibition resulted in the failure of the formation of egg cylinder.