Molecular insights into insulin-like signaling and its positive role in growth of the bivalve Mulinia lateralis

In terrestrial animals, the somatotropic axis, comprising growth hormone (GH) and insulin-like growth factors (IGFs), is pivotal in regulating growth and development. Marine mollusks play a vital role in the aquaculture industry, and understanding the molecular mechanisms of mollusk growth is of great value to breeding fast-growing and high-yielding varieties. Unlike terrestrial animals, marine mollusks lack a model species for laboratory breeding, leaving many growth-related genes unvalidated. The dwarf surf clam Mulinia lateralis, with its small size, short breeding cycle, and ease of cultivation in laboratory settings, serves as an ideal model for investigating growth regulation. This study is the first systematic identification of genes related to M. lateralis growth, with 195 differentially expressed genes (DEGs) being found between fast- and slow-growing individuals through transcriptome comparison. KEGG analysis revealed significant enrichment of the insulin-like signaling pathway, and the insulin-like peptide (ILP) was the most significantly upregulated. As the insulin signaling pathway is activated by ligand–receptor binding, we further characterized and functionally validated mlILP and its receptor, the insulin receptor-related receptor (mlIRR). RNA interference (RNAi)-mediated knockdown of mlILP or mlIRR resulted in growth retardation, confirming their positive roles in growth regulation. Notably, silencing of these two genes caused significant upregulation of downstream genes, suggesting a compensatory mechanism for maintaining cell homeostasis. Our findings advance the understanding of growth regulation in mollusks and provide candidate genes for scallop breeding aiming at growth improvement.