Identification of novel target genes of CeTwist and CeE/DA

Dev Biol. 2006 May 15;293(2):486-98. doi: 10.1016/j.ydbio.2005.10.011. Epub 2006 Feb 15.

Abstract

Twist, a basic helix-loop-helix (bHLH) transcription factor, plays an important role in mesoderm development in many organisms, including C. elegans where CeTwist is required to direct cell fate specifications of a subset of mesodermal cells. Although several target genes of CeTwist have been identified, how this protein accomplishes its function is unclear. In addition, several human genes whose mutations cause different syndromes of craniosynostosis (premature fusion of cranial sutures) have homologues in the CeTwist pathway. Identification of novel target genes of CeTwist will shed more light on the functions of CeTwist in mesoderm development, and the corresponding human homologues will be good candidates for related syndromes with unidentified mutated genes. In our study, both CeTwist and its heterodimeric partner, CeE/DA, were overexpressed from the inducible heat-shock promoter, and potential target genes were detected with Affymetrix oligonucleotide microarrays. Using transcriptional GFP reporters, we found 11 genes were expressed in cells coincident with known CeTwist target gene products. Based on subsequent validation experiments, 9 genes were defined as novel CeTwist and CeE/DA targets. Human homologues of two of these genes might be involved in craniofacial diseases, which further validates C. elegans as a good model organism for providing insights into these disorders.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA, Helminth / genetics
  • Female
  • Gene Expression Profiling
  • Genes, Helminth*
  • Green Fluorescent Proteins / genetics
  • Humans
  • Male
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Recombinant Proteins / genetics
  • Twist-Related Protein 1 / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • HLH-2 protein, C elegans
  • HLH-8 protein, C elegans
  • Recombinant Proteins
  • Twist-Related Protein 1
  • Green Fluorescent Proteins