Role of Fra-2/AP-1 in Myogenic Progenitor Cells

Components of AP-1 have dynamic expression profiles during myogenesis in C2C12 cells, the expression profile of AP-1 is different among proliferative myoblasts, differentiating myoblasts, differentiated myotubes and reserve cells, indicating context-dependent spatial and temporal roles. We found that the expression profile of Fra-2/AP-1 is also dynamic in cultured single fibers, which harbor satellite cells. We observed Pax7 mRNA level went down accompanied with precocious differentiation upon konckdown of Fra-2, suggesting that Fra-2 may play a role in determining the fate of satellite cells by modifying the expression of the key specification factor, Pax7. In addition, inhibition of ERK 1/2 MAPK pathway, a known upstream kinase of Fra-2, led to the loss of Fra-2 and Pax7 expression at protein level. Furthermore, loss of function using siRNA technology indicated that the effect of AP-1 on Notch signaling and its downstream target genes in satellite cells is Fra-2 specific, while c-Jun did not have the same effect. Fra-2 was also found to modulate the expression of Sbno1, a novel downstream effector of Notch signaling in myogenic cells. In conclusion, this work provides some insight into the role of Fra-2/AP-1 in the regulation of satellite cells by looking into how Fra-2 might determine the fate of satellite cells by modulating the expression of Pax7.