Quantifying tissue development

Biology, dauntingly complex as it is, nevertheless is slowly becoming more quantitative and thus more amenable to testable models and predictions. For example, an embryo’s various organs and body parts develop at different times and at different rates. How can one come up with a rigorous model for the process? James Sharpe (Centre for Genomic Regulation, Barcelona, Spain) and his colleagues are beginning to address that question with a new imaging technique: time-lapse optical projection tomography. Their setup involves taking live tissue from a mouse embryo and transferring it on tungsten pins to a nutrient- and oxygen-rich chamber. The pins are on a mount that is magnetically attached to a micromanipulator, which rotates the tissue through 360° in 100—200 steps. Labeling gene activity within the tissue with green fluorescent protein and using deep-penetrating 800-nm light, the researchers acquired a full set of images every 15 minutes. The images here of three-dimensional surface renderings show the dynamic activity of a gene involved in controlling development of the limb, as it buds out from abdominal tissue, at 0, 13, and 19 hours. The researchers quantified the global dynamics by measuring the surface expansion through tissue velocity vector fields. Surprisingly, the limb buds didn’t simply expand radially but twisted and showed other spatial variations as they grew. In other experiments, Sharpe and company imaged dynamic changes in spatial gene-expression patterns in growing limbs and studied the early development of embryonic mouse eyes. (M. J. Boot et al. , Nat. Methods , advance online publication, doi:10.1038/nmeth.1219, 30 May 2008.)