Nestin enhancer requirements for expression in normal and injured adult CNS

J Neurosci Res. 2002 Sep 15;69(6):784-94. doi: 10.1002/jnr.10376.


The nestin gene is expressed in many CNS stem/progenitor cells, both in the embryo and the adult, and nestin is used commonly as a marker for these cells. In this report we analyze nestin enhancer requirements in the adult CNS, using transgenic mice carrying reporter genes linked to three different nestin enhancer constructs: the genomic rat nestin gene and 5 kb of upstream nestin sequence (NesPlacZ/3), 636 bp of the rat nestin second intron (E/nestin:EGFP), and a corresponding 714 bp region from the human second intron (Nes714tk/lacZ). NesPlacZ/3 and E/nestin:EGFP mice showed reporter gene expression in stem cell-containing regions of brain and spinal cord during normal conditions. NesPlacZ/3 and E/nestin:EGFP mice showed increased expression in spinal cord after injury and NesPlacZ/3 mice displayed elevated expression in the periventricular area of the brain after injury, which was not the case for the E/nestin:EGFP mice. In contrast, no expression in adult CNS in vivo was seen in the Nes714tk/lacZ mice carrying the human enhancer, neither during normal conditions nor after injury. The Nes714 tk/lacZ mice, however, expressed the reporter gene in reactive astrocytes and CNS stem cells cultured ex vivo. Collectively, this suggests a species difference for the nestin enhancer function in adult CNS and that elements outside the second intron enhancer are required for the full injury response in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Astrocytes / cytology
  • Astrocytes / physiology
  • Brain Injuries / physiopathology*
  • Enhancer Elements, Genetic / genetics*
  • Epidermal Growth Factor / genetics
  • Female
  • Gene Expression / physiology
  • Genes, Reporter
  • Humans
  • Intermediate Filament Proteins / genetics*
  • Introns / genetics
  • Lac Operon
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Nerve Tissue Proteins*
  • Nestin
  • Neurons / cytology
  • Neurons / physiology*
  • Spinal Cord Injuries / physiopathology*
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Tumor Cells, Cultured


  • Intermediate Filament Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nes protein, rat
  • Nestin
  • Epidermal Growth Factor