title: Bmp signaling exerts opposite effects on cardiac differentiation.
abstract: BACKGROUND
  The importance for Bmp signaling during embryonic stem cell differentiation into myocardial cells has been recognized. The question when and where Bmp signaling in vivo regulates myocardial differentiation has remained largely unanswered.
  
  
  OBJECTIVE
  To identify when and where Bmp signaling regulates cardiogenic differentiation.
  
  
  RESULTS
  Here we have observed that in zebrafish embryos, Bmp signaling is active in cardiac progenitor cells prior to their differentiation into cardiomyocytes. Bmp signaling is continuously required during somitogenesis within the anterior lateral plate mesoderm to induce myocardial differentiation. Surprisingly, Bmp signaling is actively repressed in differentiating myocardial cells. We identified the inhibitory Smad6a, which is expressed in the cardiac tissue, to be required to inhibit Bmp signaling and thereby promote expansion of the ventricular myocardium.
  
  
  CONCLUSIONS
  Bmp signaling exerts opposing effects on myocardial differentiation in the embryo by promoting as well as inhibiting cardiac growth.
authors.affiliation: Cardiac development and genetics group, Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, Utrecht, The Netherlands. j.bakkers@hubrecht.eu
authors.forename: Emma
authors.initials: E
authors.lastname: de Pater
authors.forename: Metamia
authors.initials: M
authors.lastname: Ciampricotti
authors.forename: Florian
authors.initials: F
authors.lastname: Priller
authors.forename: Justus
authors.initials: J
authors.lastname: Veerkamp
authors.forename: Ina
authors.initials: I
authors.lastname: Strate
authors.forename: Kelly
authors.initials: K
authors.lastname: Smith
authors.forename: Anne Karine
authors.initials: AK
authors.lastname: Lagendijk
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schilling
authors.forename: Wiebke
authors.initials: W
authors.lastname: Herzog
authors.forename: Salim
authors.initials: S
authors.lastname: Abdelilah-Seyfried
authors.forename: Matthias
authors.initials: M
authors.lastname: Hammerschmidt
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bakkers
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism*; D015398:Signal Transduction; D051905:Smad6 Protein / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D051905:Smad6 Protein; D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins; C405936:bmp2b protein, zebrafish; C486014:tbx20 protein, zebrafish; C491461:tbx2a protein, zebrafish; D030201:Activin Receptors, Type I; D052005:Bone Morphogenetic Protein Receptors, Type I; C424203:acvr1l protein, zebrafish