IGF2BP1 regulates chicken skeletal muscle development through an m6A-dependent inter-organ regulatory axis

Skeletal muscle development in poultry involves the interplay between local myogenic programs and systemic metabolism, yet the inter-organ regulatory mechanisms linking these processes remain poorly understood. Here, we identified a structural variation (SV) in the IGF2BP1 locus-encoding an m6A reader protein-that promotes chicken muscle development through a liver-to-muscle regulatory axis. In a Gushi × Anka F₂ resource population, chickens carrying the L1 allele exhibited significantly increased muscle mass accompanied by elevated serum cholesterol, triglycerides, and VLDL, indicating enhanced hepatic metabolic output. Integrative multi-omics analyses combining liver transcriptomics, co-immunoprecipitation mass spectrometry (CoIP-MS), and RNA immunoprecipitation sequencing (RIP-seq) revealed that IGF2BP1 interacts with proteins enriched in ATP synthesis and lipid metabolism while directly binding CD44 mRNA. Notably, strong positive correlations between serum lipid levels and muscle CD44 expression (r > 0.90, P < 0.01) supported the in vivo relevance of this hepatic-muscular cascade. Mechanistically, IGF2BP1 stabilized CD44 transcripts in an m6A-dependent manner, as validated by methylated RNA immunoprecipitation-qPCR (meRIP-qPCR), mRNA decay assays, and dual-luciferase reporter experiments. In primary myoblasts, CD44 overexpression accelerated cell cycle progression and enhanced migratory capacity by 1.84-fold, whereas CD44 knockdown suppressed both proliferation and migration. These findings define a novel m6A-dependent IGF2BP1-CD44 axis that bridges hepatic metabolism with myogenic programs, providing molecular targets for marker-assisted selection to improve meat production in poultry.