Screening of circRNAs Associated with Secondary Wool Follicle Development in Fine-Wool Sheep and Construction of Their ceRNA Network

Various signalling molecules and pathways critical for wool production and quality regulate wool secondary follicle (SF) development. Circular RNAs (circRNAs) regulate SF morphogenesis through a competing endogenous RNA (ceRNA) mechanism; these novel cyclic non-coding RNAs are not known to regulate the development of SFs in the foetal period of fine-wool sheep. Here, we analysed circRNA expression profiles in the foetal skin of Gansu Alpine fine-wool sheep at 10 developmental stages (E87, E90, E93, E96, E99, E102, E105, E108, E111, and E138) using RNA sequencing. Among the differentially expressed circRNAs (DE circRNAs), 173 were significantly enriched in signalling pathways related to hair follicle (HF) development, such as Wnt/β-catenin, transforming growth factor-β/Smad, Notch, and mitogen-activated protein kinase. Six HF-development-related circRNAs were expressed at different stages and potentially regulated SF development through the ceRNA network. In total, 16 DE circRNAs and their targets, 44 miRNAs, and 65 mRNAs were screened, and 88 ceRNA regulatory network pathways related to SF development were constructed. These key DE circRNAs could be candidate genes for further exploration of the molecular HF development mechanism, providing an important theoretical basis for unravelling the regulatory network of SF development in fine-wool sheep and genetic wool trait improvement.