The LIM domain protein LmFHL2 is required for nymph-adult metamorphosis of Locusta migratoria

Abstract

The four-and-a-half LIM domain protein 2 (FHL2) is a conserved transcriptional co-regulator critical for vertebrate development and metabolism, yet its roles in arthropods remain poorly understood. Here, we report the functional characterization of LmFHL2 in the migratory locust Locusta migratoria, a devastating pest reliant on precise molting cycles for growth and swarming. Phylogenetic and expression analyses revealed high conservation of LmFHL2 across insects, with predominant expression in integument and gut tissues. Temporal expression profiling showed that LmFHL2 was primarily expressed during the adult developmental stage. Notably, topical application of juvenile hormone analogue (JHA) to adult locusts resulted in significant upregulation of LmFHL2 expression levels. RNAi-mediated silencing of LmFHL2 resulted in developmental defects in L. migratoria, including molting-associated mortality, reduced body weight, and impaired wing morphogenesis. Histopathological examination showed delayed cuticle formation and disorganized fat body architecture, while integrated multi-omics analyses identified multiple differentially expressed genes and metabolites associated with amino acid, lipid, and carbohydrate metabolism. Mechanistically, knockdown of LmFHL2 disrupted core metabolic pathways—serine hydroxymethyltransferase (SHMT), phosphoenolpyruvate carboxykinase (PCK), and purine nucleoside phosphorylase (PNP), etc.—leading to significant reductions in amino acid, triglycerides, and glycogen content. These findings establish LmFHL2 as a critical regulator of cuticular remodeling and energy-related core metabolic processes during the nymph-to-adult molting transition, providing potential molecular target for pest management strategies.