Heterogeneity in progenitor cell subtypes in the ventricular zone of the zebrafish adult telencephalon

Abstract

The zebrafish has become a new model for adult neurogenesis, owing to its abundant neurogenic areas in most brain subdivisions. Radial glia-like cells, actively proliferating cells, and label-retaining progenitors have been described in these areas. In the telencephalon, this complexity is enhanced by an organization of the ventricular zone (VZ) in fast and slow-dividing domains, suggesting the existence of heterogeneous progenitor types. In this work, we studied the expression of various transgenic or immunocytochemical markers for glial cells (gfap:gfp, cyp19a1b:gfp, BLBP, and S100beta), progenitors (nestin:gfp and Sox2), and neuroblasts (PSA-NCAM) in cycling progenitors of the adult zebrafish telencephalon (identified by expression of proliferating cell nuclear antigen (PCNA), MCM5, or bromodeoxyuridine incorporation). We demonstrate the existence of distinct populations of dividing cells at the adult telencephalic VZ. Progenitors of the overall slow-cycling domains express high levels of Sox2 and nestin:gfp as well as all glial markers tested. In contrast, domains with an overall fast division rate are characterized by low or missing expression of glial markers. PCNA-positive cells in fast domains further display a morphology distinct from radial glia and co-express PSA-NCAM, suggesting that they are early neuronal precursors. In addition, the VZ contains cycling progenitors that express neither glial markers nor nestin:gfp, but are positive for Sox2 and PSA-NCAM, identifying them as committed neuroblasts. On the basis of the marker gene expression and distinct cell morphologies, we propose a classification for the dividing cell states at the zebrafish adult telencephalic VZ.

Expression of the transcription factor Olig2 in proliferating cells in the adult zebrafish telencephalon

“…Curiously and in contrast to more anterior sections, Tg(olig2:EGFP) in this more posterior location continued as a small stretch ventral of the RMS directly at the ventricle, (asterisks in Figs. 5E, G and 6F), which was identified earlier to be the location of radial glial cells (März et al, 2010). This suggests that the ventral ventricular zone of the posterior Vv harbours a specialised class of olig2-expressing cells.…”

“…Recent studies on cell proliferation in the zebrafish telencephalon focused mainly on progenitor cells located at the ventricle and on the production of new neurons and cells of the astrocytic/ radial glial lineage Grandel et al, 2006;Pellegrini et al, 2007;Lam et al, 2009;März et al, 2010). In this study, we addressed the distribution and proliferation of cells of the oligodendrocyte lineage.…”

“…6C). In the medial telencephalon, the RMS is located more dorsally and is less pronounced Grandel et al, 2006;März et al, 2010). As in more anterior regions, only a subpopulation of PCNA-positive cells expressed Tg(olig2:EGFP) (arrows in Fig.…”

“…1B and 5A-C), a region that was previously shown to be highly proliferative März et al, 2010). To map the expression of Tg(olig2:EGFP)-expressing cells in this proliferation zone, we co-stained transverse sections through the telencephalon of Tg(olig2:EGFP) transgenics with anti-GFP and anti-PCNA antibodies (Figs.…”

“…Scale bar ¼ 100 mm. we investigated the co-expression of PSA-NCAM (Seki and Arai, 1993;Hu et al, 1996), which is abundantly expressed in cells of the RMS and often associated with migrating neuroblasts März et al, 2010). Almost all Tg(olig2:EGFP) cells of the RMS co-expressed PSA-NCAM (arrowhead in Fig.…”