1. Department of Embryology, Carnegie Institution of Washington, 115 West University Parkway, Baltimore, Maryland 21210, USA
2. Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Correspondence to: Chen-Ming Fan¹ Correspondence and requests for materials should be addressed to C.M.F. (Email: fan@ciwemb.edu).

Abstract

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^{1, 2}, 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 cancer³.

1. Department of Embryology, Carnegie Institution of Washington, 115 West University Parkway, Baltimore, Maryland 21210, USA
2. Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Correspondence to: Chen-Ming Fan¹ Correspondence and requests for materials should be addressed to C.M.F. (Email: fan@ciwemb.edu).

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