From zebrafish (Danio rerio) to mouse, the function of Nfix in skeletal muscle development is partially conserved during the evolution

In amniotes, skeletal muscle is formed by different classes of myogenic precursors (embryonic, fetal myoblasts and satellite cells) that give rise to subsequent generations of muscle fibers in distinct developmental stages. Recently, genes that are differentially expressed in murine embryonic and fetal myoblasts have been identified and among all, we demonstrated that the transcription factor Nfix regulates fetal-specific transcription in developing skeletal muscle. Zebrafish muscles, though similar to mouse muscles, develop at a faster rate to enable embryos with early motility, essentially needed to escape from predators and find food. In fact, only 24 hours post fertilization (24 hpf) a functional myotome has already been formed with primary slow and fast fibers. Following this primary muscle wave, at 48 hpf, secondary slow fibers differentiate in several body locations. Until now, primary and secondary myogenic waves in zebrafish have not been correlated with their murine counterparts. By using a loss-of-function approach to specifically abrogate its function in vivo, we provide first evidence for a partial evolutionary conserved role of nfixa, the hortolog of Nfix in zebrafish, in muscle development. At variance with mouse, lack of nfixa impairs fish motility due to a strong reduction of the sarcoplasmic reticulum, whereas, much as in mouse, nfixa strongly regulates slow twitch fiber differentiation during the second myogenic wave. Despite differences in body plan organization between fish and mouse, we show here the first evidences of a conserved role for Nfix in skeletal muscle development toward a more mature and organized structure. Moreover, we highlight a new role for zebrafish nfixa in sarcoplasmic reticulum formation.