Local microenvironments versus tissue compartments in embryos — which cells are “really” moving and where are they going?

Abstract

Present knowledge of morphogenesis in warm-blooded embryos is overwhelmingly based on interpretation of static images, or analyses of cell “migration” in the absence of a tissue-based frame of reference. However, physics dictates that, in addition to local cell-autonomous motion, cells experience global tissue displacements (0.1–1.0mm length-scale). We created novel algorithms designed to isolate “true” cell crawling from the passive convection of cells via tissue motion. Our computational approach makes use of wide-field time-lapse microscopy to examine gastrulation. Embryonic cells are tagged with one fluorochrome, while ECM proteins are labeled in a different color to monitor tissue motion. The time-lapse data are mathematically separated into: local cell autonomous displacements and large-scale tissue convections. Thus, we visualize and measure embryonic cell position-fate and tissue position-fate by subtracting the “background” motion of the ECM from the apparent (total) trajectories of individual cells. The resulting data are the first to quantify, dynamically, the difference between cell autonomous motion versus translocation to new positions via passive, large-scale, tissue drift. In some regions of gastrulating embryos more than half of “total” (apparent) cell motion is due to long-range tissue displacements; and embryos display complicated regional patterns of tissue deformation. The data also suggest that autonomous “embryonic” cell motion is correlated with the direction of the maximal principal stretch of the ECM fibrils. In conclusion, proper quantification of cell “migration”, in amniote embryos, will have to account for tissue drift.