Heterogeneity and Fgf dependence of adult neural progenitors in the zebrafish telencephalon

Abstract

Adult telencephalic neurogenesis is a conserved trait of all vertebrates studied. It has been investigated in detail in rodents, but very little is known about the composition of neurogenic niches and the cellular nature of progenitors in nonmammalian vertebrates. To understand the components of the progenitor zones in the adult zebrafish telencephalon and the link between glial characteristics and progenitor state, we examined whether canonical glial markers are colocalized with proliferation markers. In the adult zebrafish telencephalon, we identify heterogeneous progenitors that reside in two distinct glial domains. We find that the glial composition of the progenitor zone is linked to its proliferative behavior. Analyzing both fast-cycling proliferating cells as well as slowly cycling progenitors, we find four distinct progenitor types characterized by differential expression of glial markers. Importantly, a significant proportion of progenitors do not display typical radial glia characteristics. By blocking or activating Fgf signaling by misexpression of a dominant negative Fgf-receptor 1 or Fgf8a, respectively, we find that ventral and dorsal progenitors in the telencephalon also differ in their requirement for Fgf signaling. Together with data on the expression of Fgf signaling components in the ventricular zone of the telencephalon, this suggests that Fgf signaling directly regulates proliferation of specific subsets of adult telencephalic progenitors in vivo. Taken together our results show that adult neural progenitor cells are heterogeneous with their respect to distribution into two distinct glial domains and their dependence upon Fgf signaling as a proliferative cue in the zebrafish telencephalon.

Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration

“…3C Barbosa et al, 2015). However, it is known that stem and progenitor cells are heterogeneous in the mammalian and zebrafish brain (Merkle et al, 2007;Kaslin et al, 2009;Ganz et al, 2010;Marz et al, 2010). The significance of heterogeneous stem cell populations in tissue regeneration remains unclear.…”

“…5). It is well established that stem cells are heterogeneous in the vertebrate brain (Shen et al, 2006;Merkle et al, 2007;Kaslin et al, 2009;Ganz et al, 2010;Marz et al, 2010) but the implications of this have yet to be uncovered. The zebrafish telencephalon regenerates well and the cerebellum can regenerate many, but not all, cell types.…”

“…Neural stem and progenitor cell populations are heterogeneous and biased in their ability to produce specific cell types in the vertebrate brain (Shen et al, 2006;Merkle et al, 2007;Kaslin et al, 2009;Ganz et al, 2010;Marz et al, 2010). The implication of heterogeneous brain stem cells for tissue regeneration is not well understood.…”

Multilineage Differentiation Potential of CNS Cell Progenitors in a Recent Developed Gilthead Seabream (Sparus aurata L.) Nervous Model

“…The adult CNS of teleost fish exhibits a high capacity for neuronal regeneration after injury [4]. Comparative studies in zebra fish and mammals show that the telencephalic Ventricular Zone (VZ) in the adult zebra fish brain generates NPCs that share characteristics with the NPCs in the mammalian SVZ: they migrate tangentially and differentiate into mature neurons into the Olfactory Bulb (OB) [5,[11][12][13][14][15]. Recently, Kishimoto et al [11] developed an in vivo fish model of telencephalic injury to demonstrate the strong ability of adult zebra fish to undergo neuronal regeneration.…”

Micromanipulation of Gene Expression in the Adult Zebrafish Brain Using Cerebroventricular Microinjection of Morpholino Oligonucleotides

“…Several stem cells zones of the adult zebrafish brain have been analyzed and it has been shown that the cells lining the ventricular surface of those regions serve as progenitor cells 9,[11][12][13][14][15][16][17][18][19][20] . Detailed analyses in the zebrafish telencephalon, for example, identified the radial glial cells, which delineate the ventricular surface of this brain region to be neurogenic progenitors 19,20 .…”