Neurogenesis in zebrafish - from embryo to adult

Abstract

Neurogenesis in the developing central nervous system consists of the induction and proliferation of neural progenitor cells and their subsequent differentiation into mature neurons. External as well as internal cues orchestrate neurogenesis in a precise temporal and spatial way. In the last 20 years, the zebrafish has proven to be an excellent model organism to study neurogenesis in the embryo. Recently, this vertebrate has also become a model for the investigation of adult neurogenesis and neural regeneration. Here, we summarize the contributions of zebrafish in neural development and adult neurogenesis.

Figure 1

Neurogenetic cascade in the embryonic thalamus of zebrafish. Highly proliferating neural epithelial Type A cells are marked by Notch, SoxB1 and Her/Hes expression. After downregulation of SoxB1/Her/Hes, thalamic progenitors become proneural Type B cells. Type C cells are immature, post-mitotic neurons, which express transcription factors, such as lhx2b and lhx9. Mature, post-mitotic Type B neurons can be identified by, for example, neurotransmitter-specific factors.

Figure 2

Anatomy of the telencephalon of the adult zebrafish. Schematic of transverse sections through the anterior (A) and posterior (B) zebrafish telencephalon indicating the different anatomical subdomains. Proliferative periventricular zones are indicated in green. Schematic was redrawn from [191]. C: Radial glial cells have long processes that reach all the way to the pial surface. Immunostaining against GFP in the Tg(GFAPGFP) line marks the radial glial cells in the telencephalon of an adult zebrafish. The section was co-stained with the proliferation marker PCNA (proliferating cell nuclear antigen) to distinguish between PCNA-negative Type I and PCNA-positive Type II cells (described in [30]). Cantd: commissural anterior, pars dorsalis; Cantv: commissural anterior, pars ventralis; Dc: central zone of the dorsal telencephalic area (D); Dd: dorsal zone of D; DEL: dorsal ependymal lining; DiV: diencephalic ventricle; Dl: lateral zone of D; Dm: medial zone of D; Dp: posterior zone of D; Lot: lateral olfactory tract; ENd: entopeduncular nucleus, dorsal part; ENv: entopeduncular nucleus, ventral part; LFB: lateral forebrain bundle; Mot: medial olfactory tract; Ppa: anterior part of parvocellular preoptic nucleus; PVZ: periventricular zone; SY: sulcus ypsiloniformis; TelV: telencephalic ventricle; Vc: ventral nucleus of the ventral telencephalic area (V); Vd: dorsal nucleus of V; Vl: lateral nucleus of V; Vp: postcommissural nucleus of V; Vs: supracommisural nucleus of V; Vv: ventral nucleus of V.

Figure 3

The major proliferative cell types in the telencephalon stem cell niche. The markers expressed by the three major cell types are indicated [30]. Notch signaling transforms proliferating Type II radial glial cells into quiescent Type I radial glial cells [151]. Note that there exists heterogeneity in the cellular composition and marker expression of stem cell niches in the telencephalon [30,140].

Figure 4

Regenerative responses to stab wound injury. Lesions introduced by a syringe needle induce a proliferative response in the periventricular region of the stabbed hemisphere. Oligodendrocytes and microglial cells accumulate at the site of lesion. The glial marker GFAP and the proliferation marker PCNA are upregulated in the lesioned hemisphere. The number of T-box brain gene 2-positive (Tbr2+) cells is increased upon injury [179]. The injury is totally healed after 30 days without traces of a glial scar. Schematic shows transverse section through the medial telencephalon.