title: TCF/Lef regulates the Gsx ParaHox gene in central nervous system development in chordates.
abstract: BACKGROUND
  The ParaHox genes play an integral role in the anterior-posterior (A-P) patterning of the nervous system and gut of most animals. The ParaHox cluster is an ideal system in which to study the evolution and regulation of developmental genes and gene clusters, as it displays similar regulatory phenomena to its sister cluster, the Hox cluster, but offers a much simpler system with only three genes.
  
  
  RESULTS
  Using Ciona intestinalis transgenics, we isolated a regulatory element upstream of Branchiostoma floridae Gsx that drives expression within the central nervous system of Ciona embryos. The minimal amphioxus enhancer region required to drive CNS expression has been identified, along with surrounding sequence that increases the efficiency of reporter expression throughout the Ciona CNS. TCF/Lef binding sites were identified and mutagenized and found to be required to drive the CNS expression. Also, individual contributions of TCF/Lef sites varied across the regulatory region, revealing a partial division of function across the Bf-Gsx-Up regulatory element. Finally, when all TCF/Lef binding sites are mutated CNS expression is not only abolished, but a latent repressive function is also unmasked.
  
  
  CONCLUSIONS
  We have identified a B. floridae Gsx upstream regulatory element that drives CNS expression within transgenic Ciona intestinalis, and have shown that this CNS expression is dependent upon TCF/Lef binding sites. We examine the evolutionary and developmental implications of these results, and discuss the possibility of TCF/Lef not only as a regulator of chordate Gsx, but as a deeply conserved regulatory factor controlling all three ParaHox genes across the Metazoa.
authors.affiliation: The Scottish Oceans Institute, Gatty Marine Laboratory, University of St Andrews, East Sands, St Andrews, Fife, KY16 8LB, UK. mgg4@st-andrews.ac.uk.
authors.forename: Myles G
authors.initials: MG
authors.lastname: Garstang
authors.affiliation: The Scottish Oceans Institute, Gatty Marine Laboratory, University of St Andrews, East Sands, St Andrews, Fife, KY16 8LB, UK. peter.osborne@lionco.com.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Osborne
authors.affiliation: The Scottish Oceans Institute, Gatty Marine Laboratory, University of St Andrews, East Sands, St Andrews, Fife, KY16 8LB, UK. dekf@st-andrews.ac.uk.
authors.forename: David E K
authors.initials: DE
authors.lastname: Ferrier
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism; D043344:Chordata / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D002938:Ciona intestinalis / Q000235:genetics / Q000254:growth & development; D019143:Evolution, Molecular; D018398:Homeodomain Proteins / Q000235:genetics*; D064175:Lancelets / Q000235:genetics; D051820:TCF Transcription Factors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D051820:TCF Transcription Factors