Canonical Wnt signalling plays many important roles during embryogenesis. During myogenesis, for example, the stabilization of β-catenin by Wnt signalling activates the transcription factor TCF/LEF-1, which upregulates the expression of myogenic regulatory factors (MRFs). On , Lin Li and co-authors identify a second role for β-catenin in myogenesis. They show that it also counteracts the effect of I-mfa, a transcriptional repressor that inhibits expression of both TCF/LEF-1 and MRFs. β-catenin interacts with I-mfa and relieves I-mfa-mediated suppression of MRFs. The authors show that endogenous I-mfa suppresses myogenesis in pluripotent P19 carcinoma stem cells by inhibiting the expression of TCF/LEF-1. β-catenin, they report, competes with I-mfa for binding to TCF/LEF-1 and thus relieves the inhibitory effects of I-mfa overexpression on myogenesis. The dual mechanism by which β-catenin regulates TCF/LEF-1-dependent transcription, suggest the authors, might help to fine-tune cellular responses to changes in Wnt signalling during development and other physiological processes and during pathological processes such as cancer.
