title: Evolution of anterior Hox regulatory elements among chordates.
abstract: BACKGROUND
  The Hox family of transcription factors has a fundamental role in segmentation pathways and axial patterning of embryonic development and their clustered organization is linked with the regulatory mechanisms governing their coordinated expression along embryonic axes. Among chordates, of particular interest are the Hox paralogous genes in groups 1-4 since their expression is coupled to the control of regional identity in the anterior nervous system, where the highest structural diversity is observed.
  
  
  RESULTS
  To investigate the degree of conservation in cis-regulatory components that form the basis of Hox expression in the anterior nervous system, we have used assays for transcriptional activity in ascidians and vertebrates to compare and contrast regulatory potential. We identified four regulatory sequences located near the CiHox1, CiHox2 and CiHox4 genes of the ascidian Ciona intestinalis which direct neural specific domains of expression. Using functional assays in Ciona and vertebrate embryos in combination with sequence analyses of enhancer fragments located in similar positions adjacent to Hox paralogy group genes, we compared the activity of these four Ciona cis-elements with a series of neural specific enhancers from the amphioxus Hox1-3 genes and from mouse Hox paralogous groups 1-4.
  
  
  CONCLUSIONS
  This analysis revealed that Kreisler and Krox20 dependent enhancers critical in segmental regulation of the hindbrain appear to be specific for the vertebrate lineage. In contrast, neural enhancers that function as Hox response elements through the action of Hox/Pbx binding motifs have been conserved during chordate evolution. The functional assays reveal that these Hox response cis-elements are recognized by the regulatory components of different and extant species. Together, our results indicate that during chordate evolution, cis-elements dependent upon Hox/Pbx regulatory complexes, are responsible for key aspects of segmental Hox expression in neural tissue and appeared with urochordates after cephalochordate divergence.
authors.affiliation: Laboratory of Cellular and Developmental Biology, Stazione Zoologica Anton Dohrn, Villa Comunale, Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Natale
authors.forename: Carrie
authors.initials: C
authors.lastname: Sims
authors.forename: Maria L
authors.initials: ML
authors.lastname: Chiusano
authors.forename: Alessandro
authors.initials: A
authors.lastname: Amoroso
authors.forename: Enrico
authors.initials: E
authors.lastname: D'Aniello
authors.forename: Laura
authors.initials: L
authors.lastname: Fucci
authors.forename: Robb
authors.initials: R
authors.lastname: Krumlauf
authors.forename: Margherita
authors.initials: M
authors.lastname: Branno
authors.forename: Annamaria
authors.initials: A
authors.lastname: Locascio
mesh_terms: D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D002938:Ciona intestinalis / Q000196:embryology* / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice
chemical_list: D018398:Homeodomain Proteins
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