Single-nucleus transcriptomics reveals cellular signatures of adaptive remodeling in the adult oyster nervous system after life-history transition

Background Non-traditional model organisms provide unique opportunities to uncover biological principles that may be inaccessible in conventional laboratory models, particularly for understanding how nervous systems adapt to major ecological and life-history transitions. The Pacific oyster Crassostrea gigas undergoes a dramatic planktonic-to-sessile transition during metamorphosis, yet the cellular and molecular basis of nervous system remodeling in the adult stage remains poorly understood. Results Here, we used single-nucleus RNA sequencing to generate a cellular atlas of the adult cerebral ganglia (CG) and visceral ganglion (VG). Comparative analyses revealed that the CG and VG are not redundant neural units but differ in cellular composition, neuronal functional programs, transcription factor regulation, and glial organization. The VG contained an expanded neuronal repertoire, enhanced signal-modulatory and effector-output programs, and a specialized metabolic glial system with conserved features, supporting its role as a principal functional ganglion in adults. By contrast, CG neurons were biased toward homeostatic and protective functions. Ganglion-specific divergence persisted among transcriptionally matched neuronal subtypes and was associated with distinct transcription factor programs. Notably, a larval apical organ-related 5-HT program was preferentially localized to the adult VG rather than the CG, the developmental descendant of the apical organ, and was coupled to a Gata3–Pitx–Uncx regulatory module. Conclusions Our findings support an adaptive model in which the functional emphasis of the oyster nervous system may shift from the larval apical organ to the adult VG after metamorphosis. This study provides cellular and molecular insights into nervous system adaptation during life-history transitions in marine invertebrates.