Active cell migration drives the unilateral movements of the anterior visceral endoderm

The anterior visceral endoderm (AVE) of the mouse embryo is a specialised extra-embryonic tissue that is essential for anterior patterning of the embryo. It is characterised by the expression of anterior markers such as Hex, Cerberus-like and Lhx1. At pre-gastrula stages, cells of the AVE are initially located at the distal tip of the embryo, but they then move unilaterally to the future anterior. This movement is essential for converting the existing proximodistal axis into an anteroposterior axis. To investigate this process, we developed a culture system capable of imaging embryos in real time with single cell resolution. Our results show that AVE cells continuously change shape and project filopodial processes in their direction of motion, suggesting that they are actively migrating. Their proximal movement stops abruptly at the junction of the epiblast and extra-embryonic ectoderm, whereupon they move laterally. Confocal microscope images show that AVE cells migrate as a single layer in direct contact with the epiblast, suggesting that this tissue might provide directional cues. Together, these results show that the anteroposterior axis is correctly positioned by the active movement of cells of the AVE in response to cues from their environment, and by a `barrier' to their movement that provides an endpoint for this migration.