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Center for Nonlinear Studies |
The de novo formation of a vascular network, in warm-blooded embryos, occurs via a self-assembly process that spans multiple length and time scales Taking advantage of wide-field, time-lapse microscopy we examined the assembly of vascular polygonal networks in whole bird embryos and in explanted embryonic mouse tissue (allantois). Primary vasculogenesis assembly steps range from cellular (1-10 µm) to tissue (100µm-1mm) level events: Individual vascular endothelial cells extend protrusions and move with respect to the extracellular matrix/surrounding tissue. Consequently, long-range, tissue-level, deformations directly influence the vascular pattern — but how this happens is poorly understood. Our computational approach allows examination of “total” cellular motion during very early embryogenesis. Embryonic cells are tagged with one fluorochrome, while extracellular matrix proteins are labeled in a different color and used as an index of tissue motion. The time-lapse data are mathematically separated into: 1) local cell autonomous displacements and 2) 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. Experimental perturbation of endothelial-specific cell-cell adhesions (VE-cadherin), during vasculogenesis, permitted dissection of the cellular motion required for vascular sprout formation. In particular, cells are shown to move actively onto vascular cords that are subject to strain via tissue deformations. Based on the empirical data we propose a simple model of preferential migration along stretched cells. Numerical simulations reveal that the model evolves into a quasi-stationary pattern containing linear segments, which interconnect above a critical volume fraction. In the quasi-stationary state the generation of new branches offsets the coarsening driven by surface tension. In agreement with empirical data, the characteristic size of the resulting polygonal pattern is density-independent within a wide range of volume fractions. These data underscore the potential of combining physical studies with experimental embryology as a means of studying complex morphogenetic systems.
Host: Yi Jiang LANL/T-7