title: Cis-regulatory control of human GLI2 expression in the developing neural tube and limb bud.
abstract: BACKGROUND
  GLI2, a zinc finger transcription factor, mediates Sonic hedgehog signaling, a critical pathway in vertebrate embryogenesis. GLI2 has been implicated in diverse set of embryonic developmental processes, including patterning of central nervous system and limbs. In humans, mutations in GLI2 are associated with several developmental defects, including holoprosencephaly and polydactyly.
  
  
  RESULTS
  Here, we demonstrate in transient transgenic zebrafish assays, the potential of a subset of tetrapod-teleost conserved non-coding elements (CNEs) residing within human GLI2 intronic intervals to induce reporter gene expression at known regions of endogenous GLI2 transcription. The regulatory activities of these elements are observed in several embryonic domains, including neural tube and pectoral fin. Moreover, our data reveal an overlapping expression profile of duplicated copies of an enhancer during zebrafish evolution.
  
  
  CONCLUSIONS
  Our data suggest that during vertebrate history GLI2 acquired a high level of complexity in the genetic mechanisms regulating its expression during spatiotemporal patterning of the central nervous system (CNS) and limbs.
authors.affiliation: National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Rashid
authors.initials: R
authors.lastname: Minhas
authors.forename: Stefan
authors.initials: S
authors.lastname: Pauls
authors.forename: Shahid
authors.initials: S
authors.lastname: Ali
authors.forename: Laura
authors.initials: L
authors.lastname: Doglio
authors.forename: Muhammad Ramzan
authors.initials: MR
authors.lastname: Khan
authors.forename: Greg
authors.initials: G
authors.lastname: Elgar
authors.forename: Amir Ali
authors.initials: AA
authors.lastname: Abbasi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D018878:Limb Buds / Q000166:cytology / Q000196:embryology*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000096:biosynthesis* / Q000235:genetics; D000075746:Zinc Finger Protein Gli2
chemical_list: C082593:GLI2 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000075746:Zinc Finger Protein Gli2; C118355:gli2a protein, zebrafish
keywords: CNE; GLI2; comparative genomics; enhancer; gene regulation; vertebrate development