A self-limiting mechanotransduction feedback loop ensures robust organ formation

Organ morphogenesis uses mechanotransduction feedback loops to convert forces into gene expression changes that regulate cell mechanics. How these loops integrate with developmental programs to ensure robust outcomes remains unclear. We show that Yap mechanotransduction establishes a self-limiting positive feedback loop for semicircular canal formation in zebrafish. Canal development proceeds through bud initiation, extension, and fusion within the otic epithelium. Local swelling of hyaluronan-rich extracellular matrix (ECM) in the bud activates Yap in a spatial pattern. Yap increases the expression of its target, ccn1l1, promoting further ECM expansion to sustain bud extension. This feedback loop confers developmental robustness: graded ccn1l1 knockdown reduces extension rate, yet canal formation persists and fails only with strong disruption. Critically, the loop contains its own termination mechanism. During bud fusion, PKA signaling, activated by the adhesion GPCR Adgrg6, downregulates ccn1l1, ending the loop. These findings reveal how mechanotransduction loops with built-in termination provide developmental control by integrating mechanical forces, transcriptional responses, and morphogenetic outcomes.