Anoctamins mediate polymodal sensory perception and larval metamorphosis in a non-vertebrate chordate

The ocean represents a complex sensory environment, which acts as a crucible of evolution for polymodal sensory perception. The cellular and molecular bases of polymodal sensory perception in a marine environment remain enigmatic. Here, we use Ca²⁺ imaging and quantitative behavioral analysis to show that in the tunicate Ciona intestinalis, two members of the evolutionarily conserved anoctamin family (Tmem16E/Ano5 and Tmem16F/Ano6) are required for sensing chemosensory and mechanosensory metamorphic cues. We find that they modulate neuronal excitability and Ca²⁺ response kinetics in the primary sensory neurons and axial columnar cells of the papillae. Chemogenetic perturbations suggest that Ano5 and Ano6 act downstream of the primary sensory transducer molecules. Using pharmacology, we show that Ano5 and Ano6 cooperate with the inositol 1,4,5-trisphosphate (IP₃) receptor and calcium release-activated channels (CRACs) to modulate tail regression. Our results establish Ano5 and Ano6 as players in the zooplanktonic molecular toolkit that controls polymodal sensory perception in aquatic environments.