Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

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dc.contributor.authorSong, J.
dc.contributor.authorMcColl, J.
dc.contributor.authorCamp, E.
dc.contributor.authorKennerley, N.
dc.contributor.authorMok, G.
dc.contributor.authorMcCormick, D.
dc.contributor.authorGrocott, T.
dc.contributor.authorWheeler, G.
dc.contributor.authorMünsterberg, A.
dc.date.issued2014
dc.description.abstractIn vertebrate embryos, cardiac progenitor cells (CPCs) undergo long-range migration after emerging from the primitive streak during gastrulation. Together with other mesoderm progenitors, they migrate laterally and then toward the ventral midline, where they form the heart. Signals controlling the migration of different progenitor cell populations during gastrulation are poorly understood. Several pathways are involved in the epithelialto- mesenchymal transition and ingression of mesoderm cells through the primitive streak, including fibroblast growth factors and wingless-type family members (Wnt). Here we focus on early CPC migration and use live video microscopy in chicken embryos to demonstrate a role for bone morphogenetic protein (BMP)/SMA and MAD related (Smad) signaling. We identify an interaction of BMP and Wnt/glycogen synthase kinase 3 beta (GSK3β) pathways via the differential phosphorylation of Smad1. Increased BMP2 activity altered migration trajectories of prospective cardiac cells and resulted in their lateral displacement and ectopic differentiation, as they failed to reach the ventral midline. Constitutively active BMP receptors or constitutively active Smad1 mimicked this phenotype, suggesting a cell autonomous response. Expression of GSK3β, which promotes the turnover of active Smad1, rescued the BMP-induced migration phenotype. Conversely, expression of GSK3β- resistant Smad1 resulted in aberrant CPC migration trajectories. Derepression of GSK3β by dominant negative Wnt3a restored normal migration patterns in the presence of high BMP activity. The data indicate the convergence of BMP and Wnt pathways on Smad1 during the early migration of prospective cardiac cells. Overall, we reveal molecular mechanisms that contribute to the emerging paradigm of signaling pathway integration in embryo development.
dc.description.statementofresponsibilityJ. Song, J. McColl, E. Camp, N. Kennerley, G.F. Mok, D. McCormick, T. Grocott, G.N. Wheeler and A.E. Münsterberg
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2014; 111(20):7337-7342
dc.identifier.doi10.1073/pnas.1321764111
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/2440/102200
dc.language.isoen
dc.publisherProceedings of the National Academy of Sciences
dc.rights© The Author (s)
dc.source.urihttps://doi.org/10.1073/pnas.1321764111
dc.subjectMyocardium
dc.subjectHeart
dc.subjectStem Cells
dc.subjectChick Embryo
dc.subjectMesoderm
dc.subjectAnimals
dc.subjectGlycogen Synthase Kinase 3
dc.subjectSignal Transduction
dc.subjectCell Differentiation
dc.subjectCell Movement
dc.subjectGene Expression Regulation, Developmental
dc.subjectBody Patterning
dc.subjectGenes, Dominant
dc.subjectPhenotype
dc.subjectSmad1 Protein
dc.subjectPrimitive Streak
dc.subjectBone Morphogenetic Protein 2
dc.subjectWnt3A Protein
dc.titleSmad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells
dc.typeJournal article
pubs.publication-statusPublished

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