During early development mesenchymal cells migrate, rearrange, and change shape to remodel the embryo. Coordinated movements of loosely-packed mesenchymal cells in the early embryo construct the vertebrate body plan and populate tissues in preparation for the construction of muscles, connective tissue and bone, as well as the lymphatic and circulatory systems. Many genes and many cells participate in these events, but there is little experimental evidence on how genes and cells generate physical forces and integrate biochemical pathways to drive mechanical movements within embryos. The goal of this research is to investigate how genes control the physical mechanics of multicellular mesenchymal tissues by: 1) analyzing the physics of re-aggregation and the cellular mechanics responsible for rapid phases of tissue sculpting, 2) challenging cells with varied micro-environments and assessing how their behavior changes, and 3)vary levels of cell adhesion molecules and surface contractility to reveal how mesenchymal tissue spreading and engulfment are mechanically coordinated. Understanding the molecular basis of rules governing the ordered assembly of mesenchymal tissue will explain how events at the subcellular scale coordinate cell behaviors during assembly of organs and functional tissues. These findings will complement and extend efforts to understand the molecular basis of mesenchymal morphogenesis and begin the process of integrating the molecular machinery into larger "morphogenetic" processes that are robust and may be adapted by tissue engineers. The cross- and interdisciplinary training resulting from this project will provide biologists and tissue engineers the ability to integrate learned concepts into a framework the will be important for both fields.
