title: Smad1 and Smad5 have distinct roles during dorsoventral patterning of the zebrafish embryo.
abstract: Smad1 and smad5 encode transcription factors that have been implicated in the transduction of signaling by the bone morphogenetic proteins Bmp2 and/or Bmp4. Here we report the characterization of Smad1 and Smad5 from the zebrafish, Danio rerio. Although smad1, smad5, bmp2b, and bmp4 are all expressed during gastrulation and although all four proteins have ventralizing activities, they appear to play distinct roles during dorsoventral pattern formation. smad1 expression starts shortly before the onset of gastrulation. It is expressed on the ventral side of the embryo, whereas smad5 transcripts are both maternally and zygotically provided and ubiquitously distributed. Injection studies and mutant analyses suggest that the ventral smad1 expression is positively regulated by Bmp2b, but not by Bmp4 signaling, whereas smad5 expression is independent of Bmp2b. Also, the dorsalized phenotype of bmp2b-mutant embryos can be rescued by exogenous Smad1, but not by Smad5. Together, these data suggest that smad1 acts later than smad5 and is itself a transcriptional target of Smad5-mediated Bmp2b signaling. During later stages of development, smad1 is expressed in eyes, dorsal cells of rhombomeres 1, 3, and 5, and somites, with highest mRNA levels in the presumptive sclerotome and adaxial regions near the notochord. Injection experiments indicate that this somitic smad1 expression is positively regulated by hedgehog signaling from the dorsal midline, thus perhaps accounting for the recently reported sonic hedgehog-induced competence of sclerotomal cells to Bmp2/4 signals.
authors.affiliation: Max-Planck Institut für Immunbiologie, Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dick
authors.forename: A
authors.initials: A
authors.lastname: Meier
authors.forename: M
authors.initials: M
authors.lastname: Hammerschmidt
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins; D005123:Eye / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism*; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins; D051902:Smad5 Protein; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D010750:Phosphoproteins; D051785:Smad Proteins; D051902:Smad5 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C525813:bmp4 protein, zebrafish; C497801:smad5 protein, zebrafish; C077245:hh protein, Drosophila