MecaMorphEME · Four-dimensional physical modeling and numerical simulation of the early mouse embryo morphogenesis.
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-09-01 → 2017-08-31
- EU contribution
- €171,461
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Four-dimensional physical modeling and numerical simulation of the early mouse embryo morphogenesis.
The quantitative understanding of preimplantation mammalian development is essential to the progress of reproductive medicine. Specifically, the process of embryo selection in vitro, which relies on the assessment of blastocyst morphology, is critical to the success of implantation. While important progress on mammalian embryology was made over the past decades from a molecular biology perspective, the mechanical and physical principles governing the morphogenesis of mammalian embryos have remained largely unexplored. The project MecaMorphEME was intended to provide a first physical & numerical framework for understanding the morphogenesis of early mouse embryos, through a tight collaboration with Jean-Léon Maître, experimentalist at the time in the laboratory of Takashi Hiiragi. The project led to the development of a new physical framework describing the shape of cells in the early mouse embryo and a powerful simulation tool for calculating its predictions. This framework allowed us to describe in physical and quantitative terms the two first morphogenetic events in mammalian embryo development: the compaction at 8-cell stage and the formation of the inner-cell mass at the next round of divisions.
Data: CORDIS, © European Union
Project objective
The quantitative understanding of the early development of mammalian embryos is essential to the progress of reproductive medicine. Yet, the physical and mechanical principles governing their morphogenesis remain largely unknown. Early mouse embryos self-organize by a succession of cell divisions, deformations and rearrangements, leading ultimately to the specification of two distinct cell lineages, segregated in inside and outside layers. Mechanical forces are therefore as important as biochemical activity in this process and precise 4-dimensional imaging of cells within the embryo reveals intense surface dynamics, regulated by contractile and adhesion proteins. However, our understanding of early embryos development still lacks a precise physical model integrating a dynamic description of the mechanical forces controlling cell shape and cell-cell adhesion.I will design a 4D physical model of the early mouse embryo providing accurate cell dynamics predictions. Cell shapes are primarily controlled by the actomyosin cortex and they will be described using recently developed cortical active shell theories. To represent accurately cell-cell adhesion dynamics, I will consider the crosstalk between cortical and adhesion proteins activities. Importantly, this model will be designed in close collaboration with an experimental group expert in the biophysical characterization of the mouse embryo, to incorporate measured mechanical parameters and molecular regulation mechanisms. Our model will be refined through cycles of theoretical predictions and experimental validations to uncover the principles of early mammalian embryos development and, more specifically, the mechanism of cell internalization at the 8 to 16 cells transition. This interdisciplinary project, at the interface between physical modeling and developmental biology will provide a unique and accurate biophysical framework for understanding the morphogenesis of early mammalian embryos.
Original text from CORDIS.
Participants
- EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergCoordinatorGermany
Links
- View on CORDIS
- DOI: 10.3030/656306
- https://web.archive.org/web/20180824030144/https://www.virtual-embryo.com/
Data: CORDIS, © European Union