Wnt/β-catenin says shape that again

June 19
Repeated morphogenetic modules may be reinforced through morphogenetic prediction error—the discrepancy between an executed tissue deformation and its prediction given a particular bioelectric–transcriptional state—but direct evidence for such a movement-based, value-free teaching cue has been scarce. Using optogenetic actuators and Gaussia-luciferase reporters during zebrafish tail-bud elongation, we trained embryos on a mechanical discrimination paradigm and discovered that pulsatile Wnt/β-catenin activity in the posterior presomitic mesoderm is essential for learning, and that Wnt amplitude tracks cell intercalation dynamics, but not mitogen-linked growth reward, during the choice assay. The movement-related Wnt signal waned across training sessions, surged when an unfamiliar acoustic vibration was applied, and selectively strengthened cue–actomyosin contractility pairings; these results are consistent with Wnt encoding a value-free morphogenetic prediction error. A dual-controller framework combining a value-based module (FGF-mediated growth prediction error in lateral plate mesoderm) with a value-free module (morphogenetic prediction error in posterior Wnt) mastered the task more rapidly than a sole value-based controller and highlighted a predominant role for posterior Wnt during late consolidation. Our findings indicate that movement-linked Wnt pulses in the posterior axis, and likely in other paraxial regions, deliver a value-free instructional signal that reinforces state–movement associations, biasing tissues toward repetition of successful shape changes. Morphogenetic prediction error may thus constitute the mechanistic substrate for habitual patterning behaviour in developing and regenerating systems.