Sox2 Regulates Lateral Line Morphogenesis via Yap/Taz-Mediated Mechanotransduction

Organ morphogenesis relies on a tightly regulated interplay between cell proliferation, migration, and differentiation. Emerging evidence suggests that mechanical forces act alongside molecular signals to orchestrate tissue patterning, yet how these diverse inputs are integrated remains poorly understood. The zebrafish posterior lateral line offers a powerful in vivo model for studying how cellular behaviors and mechanosensitive signaling are spatiotemporally coordinated during organogenesis. Here, we identify the transcription factor Sox2 as a key regulator of lateral line morphogenesis, influencing the positioning, size, and number of neuromasts, the sensory organs of the lateral line. Loss of Sox2 leads to increased lateral line primordium cell proliferation, disrupted rosette assembly, and smaller neuromasts positioned more posteriorly along the body axis, while Sox2 overexpression produces opposite phenotypes. Sox2 functions in part by repressing Yap/Taz signaling in the primordium. Reduced Yap/Taz activity results in more anterior neuromast deposition and premature termination of primordium migration. Furthermore, we show that as the primordium expands through cell-proliferation, increased cell-junction tension activates Yap/Taz, thereby influencing lateral line development. Reducing overproliferation in sox2 ^-/- embryos diminishes the elevated Yap/Taz activity, supporting a model in which Sox2 limits proliferation to suppress Yap/Taz signaling and ensure proper primordium morphogenesis. These findings uncover a biomechanical feedback loop in which Sox2 regulates morphogenesis by modulating tissue tension and mechanosensitive signaling.