ORIENTED CELL MOVEMENTS IN EMBRYOGENESIS

SUMMARY The morphogenetic migratory activities of embryonic cells may be controlled by either of two recognized mechanisms, both involving interactions at the cell surface. By means of “selective fixation,” cells move from their site of origin, randomly and indiscriminately, over surfaces in the environment, until they chance upon a region having specific co-aptive properties, at which point further migration is inhibited. Several examples of this type of cell behaviour are described. By “selective conduction,” cells are guided from one point to another in non-random, smoothly oriented movements, by directional cues along the migration route. Although it has been clearly demonstrated that cells in vitro can accept orienting information from the surface configuration of the substratum upon which they move, there is no direct or compelling evidence that such oriented substrata do exist and exert their directional effects on migrating cells in the intact embryo. Crucial evidence that any given cell movement in vivo is controlled by contact guidance requires a system in which (1) cells in situ can be tracked in their movements, moment by moment, to determine whether they take a direct, non-random route; (2) the properties of the natural substratum upon which the cells migrate can be determined; and (3) the migratory cells and their natural substratum can be manipulated experimentally. It is suggested that the migratory behaviour of the precardiac mesoderm cells upon their endodermal substratum might provide a system which satisfies these criteria. The paired heart-forming regions of the early chick embryo are composed primarily of discrete clusters of mesoderm cells. On time-lapse films taken of embryos developing in culture, these precardiac clusters can be identified and traced in their movements from their initial sites in the heart primordia until they fuse with the forming tubular heart. Each cluster migrates actively on its endodermal substratum and is simultaneously carried toward the midline by the ventro-mesiad folding movements of the endoderm as that layer forms the floor of the foregut. Initially (stages four to six-plus), the movements of the mesoderm clusters are randomly oriented and unrelated to each other. However, there gradually emerges a crescentic spatial pattern, the position of each cluster within this crescent being related to its route of migration and future position in the heart. At stage six to seven, after the precardiac material becomes organized, the clusters are subjected to an orienting influence which causes them to move smoothly and directly up the cardiogenic crescent into the midline site of heart formation. At this time, bands of endoderm cells underlying the forming mesoderm crescent change in outline from squamous irregular polygonal shapes to spindle-shaped or lunate columnar cells. These elongated endoderm cells form a “path” in the appropriate place and at the correct time to provide the required orienting influence for the migrating mesoderm clusters. It is suggested that in the early phase the mesoderm in the heart-forming regions is sorted out on the basis of evolving tissue affinities, or selective adhesion, while contact guidance becomes effective later in directing the cell clusters from lateral to midline positions. No evidence is presented in support of this interpretation other than the correlation in time and direction of the oriented endoderm and mesoderm. An experimental approach for testing the supposed causal relationship is proposed.