CSX/NKX2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells

J. Biol. Chem (Papers In Press, published online ahead of print January 13, 2005)

CSX/NKX2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro

ABSTRACT:
CSX/Nkx2.5 transcription factor plays a pivotal role in cardiac development, however, its role in development and differentiation of other organs has not been investigated. In this study, we used C2C12 myoblasts and human fetal primary myoblasts to investigate the function of Nkx2.5 in skeletal myogenesis. The expression levels of Nkx2.5 decreased as C2C12 myoblasts elongated and fused to form myotubes. Expression of human NKX2.5 in C2C12 myoblasts inhibited myocyte differentiation and myotube formation, and up-regulated Gata4 and Tbx5 expression. Expression of NKX2.5 in terminally differentiated C2C12 myotubes resulted in a change in morphology and breakdown into smaller myotubes. Furthermore, over-expression of NKX2.5 in C2C12 cells and primary cultures of human fetal myoblasts led to differentiation of myoblasts into neuron-like cells and expression of neuronal markers. This study sheds light on previously unknown non-cardiac functions of Nkx2.5 transcription factor.