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Self-organisation and symmetry breaking in the early mouse embryo

Supervisor: Magdalena Zernicka-Goetz

The first morphogenetic transition in the early mouse embryo development happens two days after fertilisation, at the 8-cell stage, and includes the morphological cell compaction, as well as the establishment of apico-basal polarisation. These are remarkably important events for whole subsequent development from two aspects: 1) they lay the foundation for the formation of blastocyst - a structure that allow the embryo to implant into the uterus; 2) the emergence of apical domain allows the bifurcation of the first two lineages - Inner cell mass (ICM) that gives rise to the new organism as well as the yolk sac; Trophectoderm that will give rise to the placenta. The question of what triggers compaction and polarisation is therefore fundamental towards understanding the first cell fate decisions in the mouse embryo. Our lab has recently identified Phospholipase C - Protein kinase C (PKC) pathway as an essential factor for triggering both compaction and polarisation at the 8-cell stage (Zhu et al, Nature Communications, 2017). However how PLC-PKC get activated at the 8-cell stage remains unexplored. In this project, we aim to use mouse embryos and variety of new novel approaches to reveal the upstream activator for PLC-PKC pathway, which will allow us to further deciphering the mechanism that triggers the morphogenetic as well as cell fate transition at the 8-cell stage. 

Relevant references

Harrison SE, Sozen B, Christodoulou N, Kyprianou C and Zernicka-Goetz M (2017). Assembly of embryonic and extra-embryonic stem cells to mimic embryogenesis in vitro. Science. Mar 2. pii: eaal1810. doi: 10.1126/science.aal1810.

Zhu M, Leung CY, Shahbazi MN and Zernicka-Goetz M. (2017). Actomyosin polarisation through PLC-PKC triggers symmetry breaking of the mouse embryo. Nat Commun. Oct 13;8(1):921. doi: 10.1038/s41467-017-00977-8. PMID:29030553 

Shahbazi MN Jedrusik A, Vuoristo S, Recher G, Hupalowska A, Bolton V, Fogarty N, Campbell A, Gasparini LD, Ilic D, Khalaf Y Niakan KK, Fishel S and Zernicka-Goetz M. (2016).  Human embryo implantation morphogenesis and self-organization in the absence of maternal tissues. Nature Cell Biology, 18(6):700-8. doi: 10.1038/ncb3347