Regulative feedback in pattern formation: towards a general relativistic theory of positional information.

Positional specification by morphogen gradients is traditionally viewed as a two-step process. A gradient is formed and then interpreted, providing a spatial metric independent of the target tissue, similar to the concept of space in classical mechanics. However, the formation and interpretation of gradients are coupled, dynamic processes. We introduce a conceptual framework for positional specification in which cellular activity feeds back on positional information encoded by gradients, analogous to the feedback between mass-energy distribution and the geometry of space-time in Einstein's general theory of relativity. We discuss how such general relativistic positional information (GRPI) can guide systems-level approaches to pattern formation.