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.
Chen
Alice E
AE
Department of Embryology, Carnegie Institution of Washington, 115 West University Parkway, Baltimore, Maryland 21210, USA.
Ginty
David D
DD
Fan
Chen-Ming
CM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D046149:Embryo Culture Techniques; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000196:embryology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D017570:MyoD Protein / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; C068686:Pax3 protein, mouse; C070835:PAX1 transcription factor; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases