her5expression reveals a pool of neural stem cells in the adult zebrafish midbrain

Abstract

Current models of vertebrate adult neural stem cells are largely restricted to the rodent forebrain. To extract the general mechanisms of neural stem cell biology, we sought to identify new adult stem cell populations, in other model systems and/or brain areas. The teleost zebrafish appears to be an ideal system, as cell proliferation in the adult zebrafish brain is found in many more niches than in the mammalian brain. As a starting point towards identifying stem cell populations in this system, we used an embryonic neural stem cell marker, the E(spl) bHLH transcription factor Her5. We demonstrate that her5 expression is not restricted to embryonic neural progenitors, but also defines in the adult zebrafish brain a new proliferation zone at the junction between the mid-and hindbrain. We show that adult her5-expressing cells proliferate slowly, self-renew and express neural stem cell markers. Finally, using in vivo lineage tracing in her5:gfp transgenic animals, we demonstrate that the her5-positive population is multipotent, giving rise in situ to differentiated neurons and glia that populate the basal midbrain. Our findings conclusively identify a new population of adult neural stem cells, as well as their fate and their endogenous environment, in the intact vertebrate brain. This cell population, located outside the forebrain, provides a powerful model to assess the general mechanisms of vertebrate neural stem cell biology. In addition, the first transcription factor characteristic of this cell population, Her5, points to the E(Spl) as a promising family of candidate adult neural stem cell regulators.

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

“…Intraperitoneal injection of BrdU was performed as described in Chapouton et al (2006) cumulatively for 5 days and followed by a 4-week chase, after which fish were sacrificed and further processed as described (Lam et al, 2009). …”

Radial glia and neural stem cells

“…Since, apparently, in physiological conditions, adult mammals need to generate only olfactory bulb interneurons, which in all vertebrates use a specialized form of glial tracks Curtis et al 2007;Doetsch and Scharff 2001;Perez-Canellas et al 1997); progenitor cells no longer need a long basal process to guide the migration of newly-generated neurons. Notably, in vertebrates that undergo widespread adult neurogenesis, like fish, reptiles and amphibians, radial glia persists during adult life Alvarez-Buylla 1990;Chapouton et al 2006;Echeverri and Tanaka 2002;Garcia-Verdugo et al 2002;Grandel et al 2006). Consistently with the idea that the conversion of radial glia into TypeB cells is mainly a morphological change, the two cell types share molecular regulatory mechanisms, like the neurogenic role of the transcription factor Pax6.…”

Notch Activity Levels Control the Balance between Quiescence and Recruitment of Adult Neural Stem Cells

“…In the adult rodent dentate gyrus, astrocytes with a radial process bordering the subgranular zone (SGZ) serve as the NSCs (Seri et al, 2001(Seri et al, , 2004. Finally, throughout the brain of adult zebrafish Chapouton et al, 2006Chapouton et al, , 2007Grandel et al, 2006), some radial glial cells lining the ventricular zone (VZ) divide and can generate neurons Pellegrini et al, 2007;März et al, 2010).…”