title: Bmp2b and Oep promote early myocardial differentiation through their regulation of gata5.
abstract: Members of both the bone morphogenetic protein (Bmp) and EGF-CFC families have been implicated in vertebrate myocardial development. Zebrafish swirl (swr) encodes Bmp2b, a member of the Bmp family required for patterning the dorsoventral axis. Zebrafish one-eyed pinhead (oep) encodes a maternally and zygotically expressed member of the EGF-CFC family essential for Nodal signaling. Both swr/bmp2b and oep mutants exhibit severe defects in myocardial development. swr/bmp2b mutants exhibit reduced or absent expression of nkx2.5, an early marker of the myocardial precursors. Embryos lacking zygotic oep (Zoep mutants) display cardia bifida and, as we show here, also display reduced or absent nkx2.5 expression. Recently, we have demonstrated that the zinc finger transcription factor Gata5 is an essential regulator of nkx2.5 expression. In this paper, we investigate the relationships between bmp2b, oep, gata5, and nkx2.5. We show that both swr/bmp2b and Zoep mutants exhibit defects in gata5 expression in the myocardial precursors. Forced expression of gata5 in swr/bmp2b and Zoep mutants restores robust nkx2.5 expression. Moreover, overexpression of gata5 in Zoep mutants restores expression of cmlc1, a myocardial sarcomeric gene. These results indicate that both Bmp2b and Oep regulate gata5 expression in the myocardial precursors, and that Gata5 does not require Bmp2b or Oep to promote early myocardial differentiation. We conclude that Bmp2b and Oep function at least partly through Gata5 to regulate nkx2.5 expression and promote myocardial differentiation. We integrate these and other data to propose a pathway of the molecular events regulating early myocardial differentiation in zebrafish.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-0448, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Reiter
authors.forename: H
authors.initials: H
authors.lastname: Verkade
authors.forename: D Y
authors.initials: DY
authors.lastname: Stainier
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004815:Epidermal Growth Factor; D050992:GATA5 Transcription Factor; D058851:GPI-Linked Proteins; D005775:Gastrula; D015870:Gene Expression; D006133:Growth Substances; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009154:Mutation; D009206:Myocardium / Q000166:cytology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism*; D029867:Xenopus Proteins; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C491268:CFC1 protein, human; D004268:DNA-Binding Proteins; D050992:GATA5 Transcription Factor; D058851:GPI-Linked Proteins; D006133:Growth Substances; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C405936:bmp2b protein, zebrafish; C494754:gata5 protein, zebrafish; C110484:tdgf1 protein, zebrafish; C096788:tdgf1.3 protein, Xenopus; D004815:Epidermal Growth Factor