In the earliest cardiac and skeletal muscle progenitor cells, we have identified a cluster of miRNAs, miR-322/503. In human miR-322 is also known as miR-424. This cluster of miRNAs drive precocious cardiomyocyte differentiation in embryonic stem cells, bringing the appearance of spontaneously contracting cells 3 days earlier. We have identified one of the molecular targets of miR-322(424)/503, Celfl/CUGBPl. miR-322(424)/503 negatively regulates Celfl expression. miR-322(424)/503 and Celfl have a reverse-correlation during development, with miR-322(424)/503 chiefly in the heart and skeletal muscles, and Celfl in the brain. Celfl is a major factor for myotonic dystrophy 1 pathogenesis where it cause muscle wasting and degeneration. miR-322(424)/503 is a novel agent which may be used to treat heart and skeletal muscle loss, injury and diseases.