An alternative model for cell sheet migration on fibronectin during heart formation

The emergence of animal form and function depends on cell migrations in the embryo. Some migrations are accomplished by cells individually, and the mechanism of movement is predictable by contemporary models of cell adhesion and cytoskeletal function. However, other migrations occur that involve layers or sheets of cells connected by junctions, and the mechanism of migration is obscure. An example is the precardiac mesoderm, an epithelium that migrates anteriorly and ventrally in the early amniote embryo to the position of heart formation. It moves upon and is influenced by the adjacent endoderm, which has produced an extracellular matrix. The matrix contains the cell adhesion and cytoskeleton-activating glycoprotein fibronectin. Some immunolocalization studies have reported that fibronectin is arrayed in an anterior-to-posterior gradient, and it has been suggested that directional migration results from a haptotactic response of each cell to the gradient, a model derived from and supported by experiments with individual cells in culture. However, we have produced evidence from immunostaining that suggests fibronectin is arrayed as a localized anterior patch rather than a gradient. We propose an alternative model for precardiac epithelial migration in which only the anterior cells attach effectively to fibronectin. Thus adhered, their cytoskeletal contractile activity generates force which propagates throughout the layer of connected cells, and efficiently pulls them in the proper direction, following the bending and extending movements of the foregut, notochord and other structures of the head. Theoretical implications of the two models are discussed.