Gfap‐positive radial glial cells are an essential progenitor population for later‐born neurons and glia in the zebrafish spinal cord. Issue 7 (21st April 2016)

• Record Type: Journal Article
• Authors: Johnson, Kimberly; Barragan, Jessica; Bashiruddin, Sarah; Smith, Cody J.; Tyrrell, Chelsea; Parsons, Michael J.; Doris, Rosemarie; Kucenas, Sarah; Downes, Gerald B.; Velez, Carla M.; Schneider, Caitlin; Sakai, Catalina; Pathak, Narendra; Anderson, Katrina; Stein, Rachael; Devoto, Stephen H.; Mumm, Jeff S.; Barresi, Michael J. F.
• Is Part Of: Glia. Volume 64:Issue 7(2016:Jul.)
• Page Start: 1170
• Page End: 1189
• Publication Date: 2016-04-21
• Subjects: radial glia -- neural stem cell -- spinal cord -- neurogenesis -- genetic ablation -- zebrafish; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.22990
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract : 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 Main Points: Gfap + radial glia are the major NSC and required for embryonic neurogenesis. Two distinct cycling NSC types exist in the embryonic spinal cord. Radial glial death is cleared by microglia and triggers a proliferative response by Sox2+ NSCs.