title: Biphasic wnt8a expression is achieved through interactions of multiple regulatory inputs.
abstract: BACKGROUND
  Vertebrate axis development depends upon wnt8a transcription in a dynamic pool of mesoderm progenitors at the posterior pole of the gastrulating embryo. The transcriptional mechanisms controlling wnt8a expression are not understood, but previous studies identified two phases of wnt8a expression in zebrafish: Nodal-dependent activation during early gastrulation (phase I) and No tail (Ntl)-dependent regulation from mid gastrula stages (phase II).
  
  
  RESULTS
  We identified two upstream cis-regulatory regions, proximal and distal, each of which possesses a promoter. The proximal regulatory region contains a margin-specific enhancer that is required for both the Nodal and Ntl responses. Phase I expression requires Nodal activation of the margin enhancer in combination with the transcription factor Zbtb4 and the distal regulatory region. Phase II expression requires Ntl regulation of the margin enhancer in the context of the proximal regulatory region. An additional mechanism is required to ensure the transition from phase I to phase II regulation. Analysis of stickleback wnt8a suggests this mechanism of regulation may be conserved.
  
  
  CONCLUSIONS
  The seemingly simple wnt8a expression pattern reflects complex interactions of multiple regulatory inputs.
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas 77843-3258, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Narayanan
authors.forename: Arne C
authors.initials: AC
authors.lastname: Lekven
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019521:Body Patterning / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005326:Fetal Proteins; D005775:Gastrula / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D008969:Molecular Sequence Data; D055457:Nodal Protein / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics / Q000502:physiology*; D023701:Smegmamorpha / Q000196:embryology / Q000378:metabolism; D013045:Species Specificity; D020825:T-Box Domain Proteins / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000098908:Brachyury Protein
chemical_list: D003598:Cytoskeletal Proteins; D017931:DNA Primers; D005326:Fetal Proteins; D055457:Nodal Protein; D020825:T-Box Domain Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000098908:Brachyury Protein; C094521:wnt8a protein, zebrafish