A major challenge for biology is to understand, mechanically as well as genetically, how embryonic cells assemble themselves into particular structures during development. Invagination, in which an epithelium folds inward, is employed in numerous contexts, including gastrulation, neurulation, and eye formation. Failure of neurulation causes serious birth defects such as spinal bifida. The deformation of a sheet of cells is driven by cytoskeletal elements, which are highly conserved among animals. Three facets of research are required. (1) Generate a highly resolved description of invagination during ascidian gastrulation, using confocal microscopy and time-lapse video microscopy. This is vital to provide sufficiently detailed description on which to base a model, to test predictions of the various hypotheses rigorously, and because it may suggest novel mechanisms by which invagination occurs. (2) Identify the cytoskeletal elements responsible for generating deformations during invagination, using experimental disruptions. (3) Employ a detailed computational model to test whether local behaviors in individual cells can account for observed kinematics.
