Cis-regulatory control of human GLI2 expression in the developing neural tube and limb bud

Dev Dyn. 2015 May;244(5):681-92. doi: 10.1002/dvdy.24266. Epub 2015 Apr 8.

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.

Keywords: CNE; GLI2; comparative genomics; enhancer; gene regulation; vertebrate development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Gene Expression Regulation, Developmental*
  • Humans
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / genetics
  • Limb Buds / cytology
  • Limb Buds / embryology*
  • Neural Tube / cytology
  • Neural Tube / embryology*
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish Proteins / biosynthesis*
  • Zebrafish Proteins / genetics
  • Zinc Finger Protein Gli2

Substances

  • GLI2 protein, human
  • Kruppel-Like Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • Zebrafish Proteins
  • Zinc Finger Protein Gli2
  • gli2a protein, zebrafish