title: BMP2 is a positive regulator of Nodal signaling during left-right axis formation in the chicken embryo.
abstract: A model of left-right axis formation in the chick involves inhibition of bone morphogenetic proteins by the antagonist Car as a mechanism of upregulating Nodal in the left lateral plate mesoderm. By contrast, expression of CFC, a competence factor, which is absolutely required for Nodal signaling in the lateral plate mesoderm is dependent on a functional BMP signaling pathway. We have therefore investigated the relationship between BMP and Nodal in further detail. We implanted BMP2 and Noggin-expressing cells into the left lateral plate and paraxial mesoderm and observed a strong upregulation of Nodal and its target genes Pitx2 and Nkx3.2. In addition Cfc, the Nodal type II receptor ActrIIa and Snr were found to depend on BMP signaling for their expression. Comparison of the expression domains of Nodal, Bmp2, Car and Cfc revealed co-expression of Nodal, Cfc and Bmp2, while Car and Nodal only partially overlapped. Ectopic application of BMP2, Nodal, and Car as well as combinations of this signaling molecules to the right lateral plate mesoderm revealed that BMP2 and Car need to synergize in order to specify left identity. We propose a novel model of left-right axis formation, which involves BMP as a positive regulator of Nodal signaling in the chick embryo.
authors.affiliation: Cell and Molecular Biology, Technical University Braunschweig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schlange
authors.forename: Hans-Henning
authors.initials: HH
authors.lastname: Arnold
authors.forename: Thomas
authors.initials: T
authors.lastname: Brand
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D008954:Models, Biological; D055457:Nodal Protein; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology*; D000097577:Homeobox Protein PITX2
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D055457:Nodal Protein; D009687:Nuclear Proteins; D011506:Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000097577:Homeobox Protein PITX2; C525719:Bmp2 protein, mouse; C431069:CFC protein, chicken; C490192:Cmar protein, mouse; C526008:Nodal protein, mouse; C104481:snail-related protein, Gallus gallus