Neurogenesis in Talpha-1 tubulin transgenic mice during development and after injury

Exp Neurol. 2006 Feb;197(2):475-85. doi: 10.1016/j.expneurol.2005.10.030. Epub 2005 Dec 5.


Talpha-1 tubulin promoter-driven EYFP expression is seen in murine neurons born as early as E9.5. Double labeling with markers for stem cells (Sox 1, Sox 2, nestin), glial progenitors (S100beta, NG2, Olig2), and neuronal progenitors (doublecortin, betaIII-tubulin, PSA-NCAM) show that Talpha-1 tubulin expression is limited to early born neurons. BrdU uptake and double labeling with neuronal progenitor markers in vivo and in vitro show that EYFP-expressing cells are postmitotic and Talpha-1 tubulin EYFP precedes the expression of MAP-2 and NeuN, and follows the expression of PSA-NCAM, doublecortin (Dcx), and betaIII-tubulin. Talpha-1 tubulin promoter-driven EYFP expression is transient and disappears in most neurons by P0. Persistent EYFP expression is mainly limited to scattered cells in the subventricular zone (SVZ), rostral migratory stream, and hippocampus. However, there are some areas that continue to express Talpha-1 tubulin in the adult without apparent neurogenesis. The number of EYFP-expressing cells declines with age indicating that Talpha-1 tubulin accurately identifies early born postmitotic neurons throughout development but less clearly in the adult. Assessment of neurogenesis after stab wound injuries in the cortex, cerebellum and spinal cord of adult animals shows no neurogenesis in most areas with an increase in BrdU incorporation in glial and other non neuronal populations. An up-regulation of Talpha-1 tubulin can be seen in certain areas unaccompanied by new neurogenesis. Our results suggest that even if stem cells proliferate their ability to generate neurons is limited and caution is warranted in attributing increased BrdU incorporation to stem cells or cells fated to be neurons even in neurogenic areas.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Brain Injuries / metabolism*
  • Bromodeoxyuridine / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Choline O-Acetyltransferase / metabolism
  • Doublecortin Protein
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry / methods
  • Indoles
  • Intermediate Filament Proteins
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neurons / metabolism*
  • Oligodendrocyte Transcription Factor 2
  • Proteoglycans / metabolism
  • Sialic Acids / metabolism
  • Stem Cells / metabolism*
  • Tubulin / genetics*


  • Antigens
  • Basic Helix-Loop-Helix Transcription Factors
  • Dcx protein, mouse
  • Doublecortin Protein
  • Glial Fibrillary Acidic Protein
  • Indoles
  • Intermediate Filament Proteins
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Neural Cell Adhesion Molecule L1
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • Proteoglycans
  • Sialic Acids
  • Tubulin
  • chondroitin sulfate proteoglycan 4
  • polysialyl neural cell adhesion molecule
  • DAPI
  • Choline O-Acetyltransferase
  • Bromodeoxyuridine