title: Depletion of Med10 enhances Wnt and suppresses Nodal signaling during zebrafish embryogenesis.
abstract: The transcriptional Mediator (MED) is a multiprotein complex that transmits information from transcription factors to RNA polymerase II (PolII) to regulate transcription. At present, the role of distinct MED subunits in general transcription versus transcription stimulated by specific signaling pathways is unclear. By means of positional cloning, we reveal that the zebrafish mutant tennismatch is a hypomorphic allele of Med10, a conserved MED middle domain subunit. Using morpholino antisense oligonucleotides, we further demonstrate that reduction of Med10 levels led to an enhancement of the Wnt signaling pathway, while also suggesting a role for Med10 in mediating the Nodal signaling pathway. In contrast to the dual roles of Med10, reduction of Med12 and Med13 levels, two MED subunits in the regulatory domain, led to an enhancement of the Wnt signaling pathway but not the Nodal pathway, while reduction of Med15 levels, a MED subunit in the tail domain, suppressed the Nodal signaling pathway but not the Wnt signaling pathway. Thus, Med10 appears to be a unique MED subunit that differentially transduces information from distinct signaling pathways during zebrafish embryogenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology/Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Xueying
authors.initials: X
authors.lastname: Lin
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rinaldo
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Fazly
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D055457:Nodal Protein; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D055457:Nodal Protein; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D029961:Zebrafish Proteins