Modelling cell migration in the mouse embryo

9 March 2010
Aaron Smith
The visceral endoderm (VE) is an epithelium of approximately 200 cells encompassing the early post-implantation mouse embryo. At embryonic day 5.5, a subset of around 20 cells differentiate into morphologically distinct tissue, known as the anterior visceral endoderm (AVE), and migrate away from the distal tip, stopping abruptly at the future anterior. This process is essential for ensuring the correct orientation of the anterior-posterior axis, and patterning of the adjacent embryonic tissue. However, the mechanisms driving this migration are not clearly understood. Indeed it is unknown whether the position of the future anterior is pre-determined, or defined by the movement of the migrating cells. Recent experiments on the mouse embryo, carried out by Dr. Shankar Srinivas (Department of Physiology, Anatomy and Genetics) have revealed the presence of multicellular ‘rosettes’ during AVE migration. We are developing a comprehensive vertex-based model of AVE migration. In this formulation cells are treated as polygons, with forces applied to their vertices. Starting with a simple 2D model, we are able to mimic rosette formation by allowing close vertices to join together. We then transfer to a more realistic geometry, and incorporate more features, including cell growth, proliferation, and T1 transitions. The model is currently being used to test various hypotheses in relation to AVE migration, such as how the direction of migration is determined, what causes migration to stop, and what role rosettes play in the process.
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