Morphogenetic forces viewed at different scales

Dr. Guy Blanchard ( Research Associate, Department of Physiology, Development and Neuroscience, School of the Biological Sciences, University of Cambridge )

Force generation and the material properties of cells and tissues are central to morphogenesis but remain difficult to measure in vivo. Insight is often limited to the ratios of mechanical properties obtained through disruptive manipulation, and the appropriate models relating stress and strain are unknown. 

In the zebrafish model, with the help of automated cell shape tracking we have mapped different cell behaviours and their contributions to tissue deformation. We infer the influence of various intrinsic and extrinsic forces and constraints from the rich spatio-temporal cell behaviour patterns, and challenge our conceptual physical models with force-mutants. We have identified the unique in vivo signatures of three forces that interact to effect the correct convergence and extension of the zebrafish neural plate. For example, cell intercalation with an active signature is a key contributor in the trunk, where cells are planar-polarised, but in the forebrain, planar cell rearrangements with a passive signature are oriented orthogonal to those in the trunk.

In the simpler Drosophila fly model we have married similar behavioural analyses with Myosin motor fluorescence intensity quantitation as a proxy for force. Epithelial cell apices show area fluctuations driven by medial myosin pulses with period lengths of 2-5 minutes, while tissue contraction proceeds over times-scales an order of magnitude longer. We link these two time-scales, showing that the convergence and extension of the germ-band is driven internally by a highly physically structured germ-band, and supplemented by a graded extrinsic pulling force. In the contractile amnioserosa tissue, we have gone furthest in measuring the mechanical properties of epithelial cells in vivo, treating the tissue as a self-measuring rheometer under cyclic loading. Using a linear viscoelastic model, we identify a fluid to solid transition associated with cell-cell adhesion stabilization and an increase in myosin density.