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Characterization of novel regulators of pluripotent stem cell organization (Magdalena Zernicka-Goetz)

Supervisor: Magdalena Zernicka-Goetz

The implantation of the mammalian embryo in the uterus is a critical developmental period that ensures the formation of the basic body plan. During this process, the 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 transition1. 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 poorly characterized.

In order to identify novel regulators of the morphogenesis of the epiblast, the Zernicka-Goetz laboratory has analyzed by 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. These studies will shed light on the molecular mechanisms responsible of the first morphological transformation of the epiblast during mammalian embryo development.

Relevant references

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

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