Gfap-positive radial glial cells are an essential progenitor population for later-born neurons and glia in the zebrafish spinal cord

Glia. 2016 Jul;64(7):1170-89. doi: 10.1002/glia.22990. Epub 2016 Apr 21.


Radial glial cells are presumptive neural stem cells (NSCs) in the developing nervous system. The direct requirement of radial glia for the generation of a diverse array of neuronal and glial subtypes, however, has not been tested. We employed two novel transgenic zebrafish lines and endogenous markers of NSCs and radial glia to show for the first time that radial glia are essential for neurogenesis during development. By using the gfap promoter to drive expression of nuclear localized mCherry we discerned two distinct radial glial-derived cell types: a major nestin+/Sox2+ subtype with strong gfap promoter activity and a minor Sox2+ subtype lacking this activity. Fate mapping studies in this line indicate that gfap+ radial glia generate later-born CoSA interneurons, secondary motorneurons, and oligodendroglia. In another transgenic line using the gfap promoter-driven expression of the nitroreductase enzyme, we induced cell autonomous ablation of gfap+ radial glia and observed a reduction in their specific derived lineages, but not Blbp+ and Sox2+/gfap-negative NSCs, which were retained and expanded at later larval stages. Moreover, we provide evidence supporting classical roles of radial glial in axon patterning, blood-brain barrier formation, and locomotion. Our results suggest that gfap+ radial glia represent the major NSC during late neurogenesis for specific lineages, and possess diverse roles to sustain the structure and function of the spinal cord. These new tools will both corroborate the predicted roles of astroglia and reveal novel roles related to development, physiology, and regeneration in the vertebrate nervous system. GLIA 2016;64:1170-1189.

Keywords: genetic ablation; neural stem cell; neurogenesis; radial glia; spinal cord; zebrafish.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Animals, Genetically Modified
  • Apoptosis / genetics
  • Cell Differentiation
  • Cell Proliferation / genetics
  • Embryo, Nonmammalian
  • Embryonic Development / genetics
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Locomotion / genetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurogenesis / physiology*
  • Neurons / physiology*
  • Spinal Cord / cytology*
  • Spinal Cord / embryology
  • Time Factors
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism


  • Glial Fibrillary Acidic Protein
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Zebrafish Proteins
  • red fluorescent protein
  • Green Fluorescent Proteins