Diverse and dynamic sources and sinks in gradient formation and directed migration.

The traditional view of directional cell migration within a tissue is that it requires a gradient of a soluble attractive chemical that is stable in space and time due to the presence of a source and a sink. However, advances in live imaging technology and the ability to study cell migration in vivo have revealed that endogenous sources and sinks are typically far more varied and complex. Both sources and sinks can be made up of multiple tissues. During long-range migrations, cells tend to divide up their trajectories and follow different source signals in each segment. When a single source signal is used repeatedly in each segment, its expression is dynamically controlled. Source signals can also originate locally from neighboring migrating cells. Sinks are important in some cases but not all, to sculpt a permissive migratory path or allow cells to move from one intermediate target to another. Migrating cells themselves can function as sinks to create a gradient out of an initially uniform chemoattractant. These diverse ways of building sources and sinks allow different cell types to navigate distinct trajectories through the same embryo even as the whole embryo undergoes the dramatic changes in cell number, position, arrangement and fate that are the essence of development.