LAUSR

Simple Summary Wool fiber diameter (WFD) is one of the most important economic traits of wool, especially in Angora rabbits. Emerging studies have been conducted on sheep and goats. However, few studies of WFD have been reported in rabbits. In our study, the diameter of coarse and fine wool and their respective hair follicles in Wan strain Angora rabbits were analyzed, and it was found that the diameter of coarse wool and hair follicles was larger than that of fine wool and hair follicles. High-throughput sequencing analysis was performed using hair follicles from coarse and fine wool. Differentially expressed genes (DEGs), including transcription factors, keratin-associated protein (KAP) and keratin (KRT) families, and extracellular matrix (ECM)-related genes, were screened. Enrichment analysis showed that skin development, epidermal cell and keratinocyte differentiation, epithelium development, and Notch and ribosome signaling pathways were important in regulating hair structure. Gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) analysis further identified six important signaling pathways and functional DEGs, including LEF1, FZD3, SMAD3, ITGB6, and BMP4. The results provide valuable data for screening molecular markers involved in hair structure and facilitating enhanced selection of super-fine wool rabbits through gene-assisted selection. Abstract Wool fiber diameter (WFD) is an important index of wool traits and the main determinant of wool quality and value. However, the genetic determinants of fiber diameter have not yet been fully elucidated. Here, coarse and fine wool of Wan strain Angora rabbits and their hair follicle traits were characterized. The results indicated significant differences in the diameters of wool fibers and their hair follicles. The RNA sequencing (RNA-Seq) technique was used to identify differences in gene expression in hair follicles between coarse and fine wool. In total, 2574 differentially expressed genes (DEGs) were found between the two hair follicle groups. Transcription factors, keratin-associated protein (KAP) and keratin (KRT) families, and ECM-related genes may control the structure of fine fibers in rabbits. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that skin development, epidermal cell and keratinocyte differentiation, epithelium development, and Notch and ribosome signaling pathways were significantly enriched, respectively. GSEA further filtered six important pathways and related core genes. PPI analysis also mined functional DEGs associated with hair structure, including LEF1, FZD3, SMAD3, ITGB6, and BMP4. Our findings provide valuable information for researching the molecular mechanisms regulating wool fiber and could facilitate enhanced selection of super-fine wool rabbits through gene-assisted selection in the future.