Neuropeptides regulate shell growth in the Mediterranean mussel (Mytilus galloprovincialis)

In bivalves, which are molluscs enclosed in a biomineralized shell, a diversity of neuropeptide precursors has been described but their involvement in shell growth has been largely neglected. Here, using a symmetric marine bivalve, the Mediterranean mussel (Mytilus galloprovincialis), we uncover a role for the neuroendocrine system and neuropeptides in shell production. We demonstrate that the mantle is rich in neuropeptide precursors and that a complex network of neuropeptide-secreting fibres innervates the mantle edge a region highly involved in shell growth. We show that shell damage and shell repair significantly modify neuropeptide gene expression in the mantle edge and the nervous ganglia (cerebropleural ganglia, CPG). When the CPG nerve commissure was severed, shell production was impaired after shell damage, and modified neuropeptide gene expression, the spatial organization of nerve fibres in the ganglia and mantle and biomineralization enzyme activity in the mantle edge. Injection of CALCIa and CALCIIa peptides rescued the impaired shell repair phenotype providing further support for their role in biomineralization. We propose that the regulatory mechanisms identified are likely to be conserved across bivalves and other shelled molluscs since they all share a similar nervous system, a common mantle biomineralization toolbox, and shell structure.