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Egg-laying performance is one of the most important economic traits in the poultry industry. Commercial layers can lay one egg almost every day during their peak-laying period. However, many Chinese indigenous chicken breeds show a relatively low egg-laying rate, even during their peak-laying period. To understand what makes the difference in egg production, we compared the hypothalamus transcriptome profiles of Lushi blue-shelled-egg chickens (LBS), a Chinese indigenous breed with low egg-laying rate and Rhode Island Red chickens (RIR), a commercial layer with relatively high egg-laying rate using RNA-seq. A total of 753 differentially expressed genes (DEGs) were obtained. Of these DEGs, 38 genes were enriched in 2 Gene Ontology (GO) terms, namely reproduction term and the reproductive process term, and 6 KEGG pathways, namely Wnt signaling pathway, Oocyte meiosis, GnRH signaling pathway, Thyroid hormone signaling pathway, Thyroid hormone synthesis and MAPK signaling pathway, which have been long known to be involved in egg production regulation. To further determine the core genes from the 38 DEGs, protein-protein interaction (PPI) network, co-expression network and transcriptional regulatory network analyses were carried out. After integrated analysis and experimental validation, 4 core genes including RAC1, MRE11A, MAP7 and SOX5 were identified as the potential core genes that are responsible for the laying-rate difference between the 2 breeds. These findings paved the way for future investigating the mechanism of egg-laying regulation and enriched the chicken reproductive regulation theory. [ABSTRACT FROM AUTHOR]