Conserved and acquired features of adult neurogenesis in the zebrafish telencephalon

Abstract

Our understanding of the cellular and molecular mechanisms underlying the adult neural stem cell state remains fragmentary. To provide new models on this issue, we searched for stem cells in the adult brain of the zebrafish. Using BrdU tracing and immunodetection of cell-type-specific markers, we demonstrate that the adult zebrafish telencephalon contains self-renewing progenitors, which show features of adult mammalian neural stem cells but distribute along the entire dorso-ventral extent of the telencephalic ventricular zone. These progenitors give rise to newborn neurons settling close to the ventricular zone within the telencephalon proper. They have no equivalent in mammals and therefore constitute a new model of adult telencephalic neural stem cells. In addition, progenitors from the ventral subpallium generate rapidly dividing progenitors and neuroblasts that reach the olfactory bulb (OB) via a rostral migratory stream and differentiate into GABAergic and TH-positive neurons. These ventral progenitors are comparable to the mammalian neural stem cells of the subependymal zone. Interestingly, dorsal and ventral progenitors in the adult telencephalon express a different combination of transcription factors than their embryonic counterparts. In the case of neurogenin1, this is due to the usage of different enhancer elements. Together, our results highlight the conserved and unique phylogenic and ontogenic features of adult neurogenesis in the zebrafish telencephalon and open the way to the identification of adult neural stem cell characters in cross-species comparative studies.

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

“…Transgenic lines failed in some instances to faithfully reproduce the expression pattern of the endogenous gene in adult animals even though they do so at embryonic stages (Blader et al, 2003;Adolf et al, 2006). Hence, we compared expression of Tg(olig2:EGFP) with endogenous olig2 mRNA.…”

“…In situ hybridization on vibratome brain slices (50 mm thickness) was performed as described in Adolf et al (2006). Fluorescent in situ hybridization and probe synthesis for olig2 and sox10 was performed as described in Lam et al (2009).…”

“…Zebrafish has recently emerged as an anamniote model in adult neural stem cell research due to its high proliferative and regenerative potential in the central nervous system (CNS) that exceeds by far mammalian capabilities (Zupanc, 2001(Zupanc, , 2006Adolf et al, 2006;Grandel et al, 2006;Chapouton et al, 2007). In the adult mammalian brain, two regions display neurogenic potential: The subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus located in the hippocampus harbour neural stem cells with astrocytic features generating predominantly neurons (Doetsch et al, 1999;Gage, 2000;Seri et al, 2001;Alvarez-Buylla and Garcia-Verdugo, 2002;Kempermann, 2002;Garcia et al, 2004).…”

“…Most studies of zebrafish adult brain proliferation concentrated on radial glia-like precursor cells located at the ventricles and on fate mapping of progenitor cells of neuronal and radial glial lineages (Zupanc and Clint, 2003;Adolf et al, 2006;Grandel et al, 2006;Pellegrini et al, 2007;Lam et al, 2009;Mä rz et al, 2010). In teleost fish, almost no classical stellate-shaped astrocytes are present and radial glialike cells are thought to fulfil astrocyte functions (Kalman, 1998).…”

Early regulation of brain aromatase (cyp19a1b) by estrogen receptors during zebrafish development

“…Indeed, they are progenitor cells ultimately capable of generating all brain cell types during mammalian embryogenesis before disappearing in adults (Gotz and Barde, 2005;Bonfanti and Peretto, 2007;Noctor et al, 2007;Malatesta et al, 2008). In other vertebrates, including teleost fish, radial cells persit in adult (Onteniente et al, 1983;Menuet et al, 2003Menuet et al, , 2005Zupanc and Clint, 2003;Pellegrini et al, 2007) and it was recently shown that radial cell can generate neurons throughout adult life in fish Adolf et al, 2006). The role of aromatase in radial glial cells is poorly understood, but estrogens are now strongly suspected to participate in the process of embryonic, adult or reparative neurogenesis (Garacia-Segura et al, 2001;Martinez-Cerdeno et al, 2006;Galea, 2008;Mouriec et al, 2008;Barha et al, 2009;De Nicola et al, 2009;Kimmel et al, 1995).…”