Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins
Copyright policy )Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins
Select members of the Wnt family of secreted glycoproteins have been implicated in inducing the myogenic determinant genes Pax3, MyoD and Myf5 during mammalian embryogenesis, but the mechanism of induction has not been defined. We describe an unexpected role for protein kinase A (PKA) signalling via CREB in this induction. Using a combination of in vitro explant assays, mutant analysis and gene delivery into mouse embryos cultured ex vivo, we demonstrate that adenylyl cyclase signalling via PKA and its target transcription factor CREB are required for Wnt-directed myogenic gene expression. Wnt proteins can also stimulate CREB-mediated transcription, providing evidence for a Wnt signalling pathway involving PKA and CREB. Our findings raise the possibility that PKA/CREB signalling may also contribute to other Wnt-regulated processes in embryonic patterning, stem cell renewal and cancer.
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
- Carnegie Institution for Science United States
- Howard Hughes Medical Institute United States
- University of the West United States
Mice, Knockout, Muscles, Gene Expression Regulation, Developmental, Muscle Proteins, Muscle Development, Cyclic AMP-Dependent Protein Kinases, Coculture Techniques, Cell Line, DNA-Binding Proteins, Embryo Culture Techniques, Mice, Mutation, Animals, Intercellular Signaling Peptides and Proteins, Paired Box Transcription Factors, Myogenic Regulatory Factor 5, Cyclic AMP Response Element-Binding Protein, PAX3 Transcription Factor, Adenylyl Cyclases, MyoD Protein
Mice, Knockout, Muscles, Gene Expression Regulation, Developmental, Muscle Proteins, Muscle Development, Cyclic AMP-Dependent Protein Kinases, Coculture Techniques, Cell Line, DNA-Binding Proteins, Embryo Culture Techniques, Mice, Mutation, Animals, Intercellular Signaling Peptides and Proteins, Paired Box Transcription Factors, Myogenic Regulatory Factor 5, Cyclic AMP Response Element-Binding Protein, PAX3 Transcription Factor, Adenylyl Cyclases, MyoD Protein
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