BACKGROUND Worker division of labor is predominant in social insects. The foraging (for) gene, which encodes cGMP‐dependent protein kinase (PKG), has been implicated in the regulation of behavioral transitions in honeybees, but information regarding its function in other social insects is scarce. RESULTS We investigated the role of the for (Sifor) gene in the red imported fire ant, Solenopsis invicta, and found that Sifor and PKG exhibited different expression patterns in different castes, body sizes, ages and tissues of fire ants, especially in foragers and nurses. Foragers displayed greater locomotor activity but showed no preference for larval or adult odors, whereas nurses showed lesser locomotor activity but had a strong preference for larval odors. We found that the expression of Sifor was significantly higher in the heads of foragers (compared to nurses). RNA interference‐mediated Sifor knockdown in foraging workers induced behavioral transition of foragers toward the nurse phenotype characterized by reduced locomotor activity and a stronger preference for larval odors. By contrast, treating nurses with 8‐Br‐cGMP, an activator of PKG, resulted in behavioral transition toward the forager phenotype characterized by higher locomotor activity but reduced preference for larval odors. CONCLUSION Our results suggest that Sifor plays a critical role in the behavioral transition between foragers and nurses of workers, which may be a promising target for RNAi‐based management of worker caste organization in S. invicta. © 2022 Society of Chemical Industry.

BACKGROUNDIn social insects, the labor division of workers is ubiquitous and controlled by genetic and environmental factors. However, how they modulate this coordinately remains poorly understood.RESULTSWe report miR‐279c‐5p participation in insulin synthesis and behavioral transition by negatively regulating Rab8A in Solenopsis invicta. Eusocial specific miR‐279c‐5p is age‐associated and highly expressed in nurse workers, and localized in the cytoplasm of neurons, where it is partly co‐localized with its target, Rab8A. We determined that miR‐279c‐5p agomir suppressed Rab8A expression in forager workers, consequently decreasing insulin content, resulting in the behavioral shift to ‘nurse‐like’ behaviors, while the decrease in miR‐279c‐5p increased Rab8A expression and increased insulin content in nurse workers, leading to the behavioral shift to ‘foraging‐like’ behaviors. Moreover, insulin could rescue the ‘foraging behavior’ induced by feeding miR‐279c‐5p to nurse workers. The overexpression and suppression of miR‐279c‐5p in vivo caused an obvious behavioral transition between foragers and nurses, and insulin synthesis was affected by miR‐279c‐5p by regulating the direct target Rab8A.CONCLUSIONWe first report that miR‐279c‐5p is a novel regulator that promotes labor division by negatively regulating the target gene Rab8A by controlling insulin production in ants. This miRNA‐mediated mechanism is significant for understanding the behavioral plasticity of social insects between complex factors and potentially provides new targets for controlling red imported fire ants.This article is protected by copyright. All rights reserved.