Flow-driven lumen remodeling and valve opening in the vas deferens

Biological ducts must transport fluids while preserving structural integrity, yet how mechano-signalling coordinates wall deformation with luminal flow in vivo remains unclear. Here we combine intravital two-photon excitation microscopy, light-sheet imaging and FRET-based kinase biosensors to resolve, in real time, ejaculation-like events in the mouse vas deferens. Acute phenylephrine stimulation elicits a sequence of luminal dynamics: an initial retrograde pressure-redistribution wave followed by a ballistic antegrade flow that propels dense sperm suspensions from proximal to distal duct. This contraction-driven flow opens a normally collapsed, highly wrinkled distal segment, driving progressive lumen expansion and unfolding of epithelial wrinkles. We show that the vas deferens actively modulates luminal geometry in response to these flow dynamics: ROCK and PKA activities in longitudinal smooth muscle are required for global contraction. By contrast, ERK activity in circumferential smooth muscle is dispensable for the ductal contraction but essential for active, flow-dependent remodelling of the distal lumen, forming the core of the mechano-signalling module that couples sperm flow to valve opening. These findings establish the vas deferens as an experimentally tractable model of ductal tissue hydraulics and reveal a mechano-signalling framework by which a tubular organ converts transient muscular input into robust, directional luminal transport.