An NF-κB - EphrinA5-Dependent Communication between NG2+ Interstitial Cells and Myoblasts Promotes Muscle Growth in Neonates

Skeletal muscle growth immediately following birth is critical for proper body posture and locomotion. However, compared with embryogenesis and adulthood, the processes regulating the maturation of neonatal muscles is considerably less clear. Studies in the 1960s predicted that neonatal muscle growth results from nuclear accretion of myoblasts preferentially at the tips of myofibers. Remarkably, little information has been added since then to resolve how myoblasts migrate to the ends of fibers. Here, we provide insight into this process by revealing a unique NF-κB-dependent communication between NG2+ interstitial cells and myoblasts. NF-κB in NG2+ cells promotes myoblast migration to the tips of myofibers through cell-cell contact. This occurs through expression of ephrinA5 from NG2+ cells, which we further deduce is an NF-κB target gene. Together, these results suggest that NF-κB plays an important role in the development of newborn muscles to ensure proper myoblast migration for fiber growth. [Display omitted] •NF-κB is activated in NG2+ interstitial cells in neonatal skeletal muscle•NF-κB functions in NG2+ interstitial cells to promote myoblast migration•The gene encoding EphrinA5 is a direct target of NF-κB•EphrinA5 from NG2+ interstitial cells promotes myoblast migration Neonatal muscle development is regulated by the accretion of myoblasts at the ends of immature fibers. Gu et al. show that NF-κB signals in NG2+ interstitial cells to induce the expression of ephrinA5, which functions to promote cell-cell contact and myoblast migration to the ends of growing fibers. NF-κB regulation of EFNA5 mediates interactions between muscle interstitial cells and myoblasts required for neonatal muscle growth.