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New regulators of pluripotent stem cell organization in the mouse and human

Supervisor: Magdalena Zernicka-Goetz

The implantation of the mammalian embryo in the uterus is a critical and yet still mysterious developmental period that ensures the formation of the basic body plan. During this process, the pluripotent embryonic tissue, or epiblast, transforms from been an apolar pluripotent group of cells, to a polarized epithelial tissue with a more restricted developmental potential.

This stage has been traditionally viewed as the “black box of development”, given the small size and inaccessibility of the embryo. New embryo culture techniques developed in the Zernicka-Goetz laboratory, together with pluripotent stem cell 3D cultures enabled the characterization of the morphological events that happen during this transition in mouse and human1,2,3. Specifically, epiblast cells polarize in response to extracellular matrix signalling to form a transitory structure with the shape of a rosette, which evolves to form a central lumen. However, the molecular mechanisms responsible for these successive morphological stages remain largely characterized.

In order to identify novel regulators of the morphogenesis of the epiblast, the Zernicka-Goetz laboratory has analyzed by RNA deep-sequencing techniques the transcriptome of the epiblast at successive stages of the implantation. The aim of this project is to characterize the functional relevance of some of the identified candidate genes using pluripotent stem cell 3D cultures and mouse early embryos. These studies will shed light on the molecular mechanisms responsible of the first morphological transformation of the epiblast during mammalian embryo development.

Relevant references

Bedzhov, I. & Zernicka-Goetz, M. Self-organizing properties of mouse pluripotent cells initiate morphogenesis upon implantation. Cell, 2014; 156 (5): 1032-1044.

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

Deglincerti A, Croft GF, Pietila LN, Zernicka-Goetz M, Siggia ED, and Brivanlou A. Self-organization of the in vitro attached human embryo. Nature, 4;533(7602):251-4. doi: 10.1038/nature17948

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