Origin of vertical shifts in phase response curves during segmentation clock entrainment

Explain the origin of the vertical phase-response-curve (PRC) shift observed when entraining the mouse segmentation clock with periodic DAPT or Chiron pulses, and determine the mechanism by which the system adjusts its internal period in response to external periodic perturbations.

Background

Microfluidic entrainment experiments demonstrate that the mouse segmentation clock can be phase-locked over a wide range of driving periods. The inferred PRCs at different driving periods show similar shapes but are vertically shifted relative to each other, a phenomenon not captured by classical PRC theory.

Understanding this vertical shift—and whether it reflects adaptive changes of the internal period or other global feedbacks—would refine theoretical models of embryonic entrainment and inform how emergent tissue-level oscillations respond to external cues.