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Self-Organising Capacity of Stem Cells during Implantation and Early Post-implantation Development: Implications for Human Development

Objective

Embryonic development progresses through successive cell fate decisions and intricate three-dimensional morphogenetic transformations. Implantation is the defining event in mammalian pregnancy during which a fundamental morphogenetic transformation is initiated: the body axes are established and the embryonic germ layers created. Despite its importance, a comprehensive understanding of the molecular mechanisms, transcriptional pathways, cellular interactions, as well as the spatio-temporal development of the embryo at implantation stages is at present lacking, due to the embryo’s inaccessibility. To overcome these limitations, we generated a culture system that allows the development of mouse implanting embryos outside of the mother. This system provides the opportunity to address how architectural features and signaling events integrate to induce the emergence of the body plan. Combining this new technology with the analysis of genetically engineered mouse embryos, the aim of this research proposal is to fill the knowledge gap between pre and post-implantation development. Single cell sequencing, two-photon microscopy, high-content forward genetic screening, and modeling will be merged with a functional assessment of embryo development in vivo to reveal the determinants of implantation and early post-implantation development. This global understanding will be employed to explore the extent to which stem cells can recapitulate embryonic development, with tremendous potential for regenerative medicine. Knowledge of the cellular and molecular mechanisms that intertwine lineage specification, developmental potential, and tissue morphogenesis will offer novel insight on the pathological causes of embryo lethality and congenital disorders. The proposed studies will shed light on this crucial yet mysterious stage of development in the mouse and, by extrapolation, offer outstanding potential to advance our understanding of human development.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /social sciences/other social sciences/social sciences interdisciplinary/sustainable development
  • /medical and health sciences/clinical medicine/embryology

Call for proposal

ERC-2014-ADG
See other projects for this call

Funding Scheme

ERC-ADG - Advanced Grant

Host institution

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 477 951

Beneficiaries (1)

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 2 477 951
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments