Gfap-positive radial glial cells are an essential progenitor population for later-born neurons and glia in the zebrafish spinal cord.
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.
Department of Biological Sciences, Smith College, Northampton, Massachusetts.|Molecular and Cellular Biology Program, University of Massachusetts, Amherst, Massachusetts.
Kimberly
K
Johnson
Department of Biological Sciences, Smith College, Northampton, Massachusetts.
Jessica
J
Barragan
Department of Biological Sciences, Smith College, Northampton, Massachusetts.
Sarah
S
Bashiruddin
Department of Biology, University of Virginia, Charlottesville, Virginia.
Cody J
CJ
Smith
Program in Neuroscience and Behavior, University of Massachusetts, Amherst, Massachusetts.
Chelsea
C
Tyrrell
Department of Surgery, Johns Hopkins University, Baltimore, Maryland.
Michael J
MJ
Parsons
Department of Biology, Wesleyan University, Middletown, Connecticut.
Rosemarie
R
Doris
Department of Biology, University of Virginia, Charlottesville, Virginia.
Sarah
S
Kucenas
Department of Biology, University of Massachusetts, Amherst, Massachusetts.
Gerald B
GB
Downes
Department of Biological Sciences, Smith College, Northampton, Massachusetts.
Carla M
CM
Velez
Department of Biological Sciences, Smith College, Northampton, Massachusetts.
Caitlin
C
Schneider
Department of Biological Sciences, Smith College, Northampton, Massachusetts.
Catalina
C
Sakai
Department of Biological Sciences, Smith College, Northampton, Massachusetts.
Narendra
N
Pathak
Department of Biological Sciences, Smith College, Northampton, Massachusetts.
Katrina
K
Anderson
Department of Biological Sciences, Smith College, Northampton, Massachusetts.
Rachael
R
Stein
Department of Biology, Wesleyan University, Middletown, Connecticut.
Stephen H
SH
Devoto
Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland.
Jeff S
JS
Mumm
Department of Biological Sciences, Smith College, Northampton, Massachusetts.|Molecular and Cellular Biology Program, University of Massachusetts, Amherst, Massachusetts.|Program in Neuroscience and Behavior, University of Massachusetts, Amherst, Massachusetts.
Michael J F
MJ
Barresi
D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000235:genetics; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology; D013997:Time Factors; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D000097573:Red Fluorescent Protein
D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D029961:Zebrafish Proteins; D000097573:Red Fluorescent Protein
genetic ablation; neural stem cell; neurogenesis; radial glia; spinal cord; zebrafish