M-TWIST IS AN INHIBITOR OF MUSCLE DIFFERENTIATION

The twist gene encodes a transcription factor containing a conserved basic helix-loop-helix domain. During development, transcription factors of this type are normally associated with the induction of differentiation. Yet the expression pattern of the murine M-twist suggests an inhibitory role during muscle differentiation. Following stable transfection of myogenic mouse cells with an M-twist expression vector, 75% of M-twist-expressing clones were impaired in their ability to differentiate. In contrast, only 15% of control clones were unable to differentiate. Treatment with antisense oligonucleotides restored differentiation capacity in a concentration-dependent manner. Control oligonucleotides had no effect. These experiments show that the mouse twist gene can act as an inhibitor of muscle differentiation and that this inhibition is reversible. (C) 1994 Academic Press, Inc.