Expression of Hairy/enhancer of split genes in neural progenitors and neurogenesis domains of the adult zebrafish brain

Abstract

All subdivisions of the adult zebrafish brain maintain niches of constitutive neurogenesis, sustained by quiescent and multipotent progenitor populations. In the telencephalon, the latter potential neural stem cells take the shape of radial glia aligned along the ventricle and are controlled by Notch signalling. With the aim of identifying new markers of this cell type and of comparing the effectors of embryonic and adult neurogenesis, we focused on the family of hairy/enhancer of split [E(spl)] genes. We report the expression of seven hairy/E(spl) (her) genes and the new helt gene in three neurogenic areas of the adult zebrafish brain (telencephalon, hypothalamus, and midbrain) in relation to radial glia, proliferation, and neurogenesis. We show that the expression of most her genes in the adult brain characterizes quiescent radial glia, whereas only few are expressed in progenitor domains engaged in active proliferation or neurogenesis. The low proliferation status of most her-positive progenitors contrasts with the embryonic nervous system, in which her genes are expressed in actively dividing progenitors. Likewise, we demonstrate largely overlapping expression domains of a set of her genes in the adult brain, which is in striking contrast to their distinct embryonic expression profiles. Overall, our data provide a consolidated map of her expression, quiescent glia, proliferation, and neurogenesis in these various subdivisions of the adult brain and suggest distinct regulation and function of Her factors in the embryonic and adult contexts.

Notch Signaling Controls Generation of Motor Neurons in the Lesioned Spinal Cord of Adult Zebrafish

“…To determine whether the pathway is active in the lesioned spinal cord, we used in situ hybridization of the hairy-related (her) genes, many of which are direct Notch target genes (Chapouton et al, 2011). Her4.1 was upregulated at 3 (data not shown) and 14 dpl (days post-lesion; when motor neuron regeneration peaks; Reimer et al, 2008) from undetectable levels, predominantly in a ventrolateral domain of the ventricular zone.…”

“…This is similar to constitutively active proliferation zones in the adult zebrafish brain. In that system, a lineage tracing study indicated that manipulations of Notch signaling only influenced the proliferation rate of progenitor cells and not the type of division (symmetrical vs asymmetrical) or cell differentiation (Chapouton et al, 2011). However, we cannot exclude that Notch has additional roles in cell fate decisions of neuroblasts during spinal cord regeneration, similar to development (Shin et al, 2007;Yeo and Chitnis, 2007;Batista et al, 2008;Kimura et al, 2008).…”

“…For instance, her4.1 expression, which is positively regulated by Notch signaling (Chapouton et al, 2011), and expression of Notch receptors was undetectable. Similarly, DAPT had no effect on proliferation and motor neuron generation.…”

Migration of neuronal precursors from the telencephalic ventricular zone into the olfactory bulb in adult zebrafish

“…On the other hand, previous studies have shown that some proneural genes in addition to ngn1 are also expressed in the ventricular telencephalic precursors that give rise to GABAergic neurons in the OB (Adolf et al, 2006). One such gene, ascl1a (the mouse Mash1 homolog), is indeed expressed along the RMS-like stripe (Chapouton et al, 2011) and is involved in the generation of GABAergic cells (Mueller et al, 2006), as is ngn1, indicating that ascl1a-expressing cells may also migrate via the RMS-like route into the OB and then differentiate into GABAergic neurons. Two weeks after the BrdU treatment, the number of labeled cells increased in the internal cellular layer (IL) consisting of GABAergic granule cells, as well as in the glomerular cellular layer (GL), where additional neuronal subtypes are present (Fig.…”

Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium

“…Notch activity, revealed by immunocytochemistry or reporter transgenes, was generally mapped to GFAP-positive or Sox2-positive NSCs, both in the SEZ and SGZ and in TAPs (Breunig et al, 2007;Ehm et al, 2010;Lugert et al, 2010;Imayoshi et al, 2010). Likewise, notch and her genes are strongly expressed in quiescent RG of the adult zebrafish pallium Chapouton et al, 2011;Ganz et al, 2010). Here, we use this experimental system to demonstrate for the first time that Notch3 activity gates NSC activation, thereby ensuring GZ homeostasis.…”