Transgenic zebrafish for studying nervous system development and regeneration

Goldman, D., Hankin, M., Li, Z., Dai, X., and Ding, J.
Transgenic Research   10(1): 21-33 (Journal)
Registered Authors
Dai, Xinhua, Goldman, Dan
alpha-1 tubulin, gene expression, nervous system development, neural stem cells, optic nerve regeneration, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified/growth & development*
  • Animals, Genetically Modified/physiology
  • Bromodeoxyuridine
  • Central Nervous System/physiology*
  • Green Fluorescent Proteins
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Luminescent Proteins/metabolism
  • Nerve Regeneration/physiology*
  • Optic Nerve/cytology
  • Optic Nerve/metabolism
  • Promoter Regions, Genetic
  • Retina/cytology
  • Retina/embryology
  • Retinal Ganglion Cells/cytology
  • Retinal Ganglion Cells/metabolism
  • Spinal Cord/cytology
  • Spinal Cord/metabolism
  • Stem Cells/cytology
  • Stem Cells/metabolism
  • Tubulin/biosynthesis
  • Tubulin/genetics
  • Zebrafish/genetics
  • Zebrafish/physiology*
11252380 Full text @ Transgenic. Res.
Alpha1 tubulin gene expression is induced in the developing and regenerating CNS of vertebrates. Therefore, alpha1 tubulin gene expression may serve as a good probe for mechanisms underlying CNS development and regeneration. One approach to identify these mechanisms is to work backwards from the genome. This requires identification of alpha1 tubulin DNA sequences that mediate its developmental and regeneration-dependent expression pattern. Therefore, we generated transgenic zebrafish harboring a fragment of the alpha1 tubulin gene driving green fluorescent protein expression (GFP). In these fish, and similar to the endogenous gene, transgene expression was dramatically induced in the developing and regenerating nervous system. Although transgene expression generally declined during maturation of the nervous system, robust GFP expression was maintained in progenitor cells in the retinal periphery, lining brain ventricles and surrounding the central canal of the spinal cord. When these cells were cultured in vitro they divided and gave rise to new neurons. We also show that optic nerve crush in adult fish re-induced transgene expression in retinal ganglion cells. These studies identified a relatively small region of the alpha1 tubulin promoter that mediates its regulated expression pattern in developing and adult fish. This promoter will be extremely useful to investigators interested in targeting gene expression to the developing or regenerating nervous system. As adult transgenic fish maintain transgene expression in neural progenitors, these fish also provide a valuable resource of labeled adult neural progenitor cells that can be studied in vivo or in vitro. Finally, these fish should provide a unique in vivo system for investigating mechanisms mediating CNS development and regeneration.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes