Coupling Vgll4b/Yap-regulated posterior cell addition with anterior vacuolation enables robust notochord elongation

Robust tissue growth control requires long-range communication between the rate of progenitor addition and tissue expansion. However, the regulatory mechanisms that couple these processes are unknown. In zebrafish, notochord morphogenesis is a driver of axis extension through both posterior progenitor addition and anterior vacuolation. To elucidate how progenitor dynamics and vacuole-driven cell expansion interact to elongate the notochord, we generated a mathematical model linking progenitor addition rate to the expansion of cells from anterior to posterior to simulate vacuolation rate. Comparing this with empirical measurements, we find that progenitor incorporation, together with vacuolation, produces a linear gradient in nearest neighbour distance. We next explored the role of YAP/TAZ in regulating progenitor addition in mutants for the YAP/TAZ inhibitor vgll4b. We find that vgll4b expression and YAP activity are enriched in posterior midline progenitors. Loss of vgll4b elevates YAP signalling, enhances progenitor addition, restricts vacuole expansion, and - after a transient buffering phase - compromises anterior-posterior axis elongation. These results support a long-range feedback mechanism linking progenitor recruitment to vacuolation, enabling the notochord to balance cellular input with volumetric expansion, thereby maintaining tissue proportions.