Figure 6. Challenges associated with the study of autonomous clocks.

(A) In most metazoans, biological events are usually phase-locked to run at the pace of the cell cycle and/or the circadian clock. The table provides examples for varying combinations of phase-locking strengths (when the strength is high, the gauge indicator points to red, or vice versa for green) and how these combinations are employed by different types of tissues during the development (first and second columns, respectively). Depending on the tissue type, autonomous clocks may display their natural frequency more easily in some (e.g., embryonic tissues) than others (e.g., proliferating progenitor tissues) (third column). We suggest experimental conditions in which novel autonomous clocks could be identified with a higher degree of confidence in interpreting their ‘autonomy’ (fourth column). (B) The flow chart illustrates a hypothetical high-throughput screen to identify novel autonomous clocks. If a prospective clock is not synchronized between cells and displays phase shift from one cell to the other (indicated by sliding blue arrows on the graph) due to the lack of an entrainment cue, then simply taking an average of rhythms in all cells may lead to a flat line. This will inevitably result in false conclusions and missed opportunities.