Functional Identification of Porcine DLK1 during Muscle Development

SIMPLE SUMMARY: Skeletal muscle is the largest tissue and serves as a protein reservoir and energy reservoir in the human and animal body. It also serves as the main metabolic activity site. The formation of skeletal muscle mainly depends on the differentiation and fusion of myocytes and other complex ordered processes; each step is regulated by various factors. In this study, we investigated the expression profiles, functional identification, and regulatory pathways of Delta-like 1 homolog (DLK1) in pigs and myocytes. We found that DLK1 was highly expressed in the muscle tissues of pigs. DLK1 promoted myocyte proliferation, migration, differentiation, fusion, and muscular hypertrophy, but suppressed muscle degradation. DLK1 also inhibited the Notch signaling pathway by regulating the expression of key factors in the pathway, thereby producing a phenotype in which DLK1 promotes muscle development. These findings provide valuable information to improve our understanding of the functional mechanisms of DLK1 that underly myogenesis to accelerate the process of animal genetic improvement. ABSTRACT: DLK1 is paternally expressed and is involved in metabolism switching, stem cell maintenance, cell proliferation, and differentiation. Porcine DLK1 was identified in our previous study as a candidate gene that regulates muscle development. In the present study, we characterized DLK1 expression in pigs, and the results showed that DLK1 was highly expressed in the muscles of pigs. In-vitro cellular tests showed that DLK1 promoted myoblast proliferation, migration, and muscular hypertrophy, and at the same time inhibited muscle degradation. The expression of myogenic and fusion markers and the formation of multinucleated myotubes were both upregulated in myoblasts with DLK1 overexpression. DLK1 levels in cultured myocytes were negatively correlated with the expression of key factors in the Notch pathway, suggesting that the suppression of Notch signaling pathways may mediate these processes. Collectively, our results suggest a biological function of DLK1 as an enhancer of muscle development by the inhibition of Notch pathways.