title: An amphioxus Gli gene reveals conservation of midline patterning and the evolution of hedgehog signalling diversity in chordates.
abstract: BACKGROUND
  Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosophila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution.
  
  
  RESULTS
  We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli gene family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3.
  
  
  CONCLUSIONS
  These data show that vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways.
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom. sebastian.shimeld@zoo.ox.ac.uk
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Shimeld
authors.forename: Marcel
authors.initials: M
authors.lastname: van den Heuvel
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dawber
authors.forename: James
authors.initials: J
authors.lastname: Briscoe
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019521:Body Patterning; D002642:Chick Embryo; D043344:Chordata / Q000235:genetics*; D004330:Drosophila / Q000196:embryology; D019143:Evolution, Molecular; D053823:Hedgehog Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics*; D010614:Pharynx / Q000196:embryology; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071676:Zinc Finger Protein GLI1
chemical_list: D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1