Figure 3.

Schematic illustration for the mechanics of self-organization and differentiation. Right: a nuclear circuit demonstrating organization during cellular differentiation. Local interactions (gene coregulation) lead to chromosomal associations that emerge cooperatively in cell-specific organization of the nucleus, which in turn feeds back to strengthen the local associations, and the self-organized system fine-tunes over time. Left: the initial state of this system is at the center of steady state 1. A perturbation, such as activation of a specific signaling pathway or shown here as induction of the transcription factor MyoD, may drive the state of the system towards the boundary of the basin of attraction of stable state 1 (locally stable state). A basin of attraction is a set of initial conditions that ultimately lead to behavior that approaches a specific state (the attractor). In other words, the system approaches cell-specific organization. When it transitions to stable state 2 (globally stable state), stability is lost and the system regains its stability only in the new steady state. In the case of MyoD, induction in MEF cells leads to a state transition into the myogenic lineage. The system is considered to be robust if its functions are still intact, regardless of whether it is in stable state 1 or 2. In an extreme case, the system may continue to transition between multiple stable state points to cope with ongoing perturbations.