Abstract

BackgroundUnlike mammals, zebrafish exhibits extensive neural regeneration after injury in adult stages of its lifetime due to the neurogenic activity of the radial glial cells. However, the genes involved in the regenerative neurogenesis response of the zebrafish brain are largely unknown. Thus, understanding the underlying principles of this regeneration capacity of the zebrafish brain is an interesting research realm that may offer vast clinical ramifications.ResultsIn this paper, we characterized the expression pattern of cxcr5 and analyzed the function of this gene during adult neurogenesis and regeneration of the zebrafish telencephalon. We found that cxcr5 was upregulated transiently in the RGCs and neurons, and the expression in the immune cells such as leukocytes was negligible during both adult neurogenesis and regeneration. We observed that the transgenic misexpression of cxcr5 in the ventricular cells using dominant negative and full-length variants of the gene resulted in altered proliferation and neurogenesis response of the RGCs. When we knocked down cxcr5 using antisense morpholinos and cerebroventricular microinjection, we observed outcomes similar to the overexpression of the dominant negative cxcr5 variant.ConclusionsThus, based on our results, we propose that cxcr5 imposes a proliferative permissiveness to the radial glial cells and is required for differentiation of the RGCs to neurons, highlighting novel roles of cxcr5 in the nervous system of vertebrates. We therefore suggest that cxcr5 is an important cue for ventricular cell proliferation and regenerative neurogenesis in the adult zebrafish telencephalon. Further studies on the role of cxcr5 in mediating neuronal replenishment have the potential to produce clinical ramifications in efforts for regenerative therapeutic applications for human neurological disorders or acute injuries.

Highlights

  • Unlike mammals, zebrafish exhibits extensive neural regeneration after injury in adult stages of its lifetime due to the neurogenic activity of the radial glial cells

  • We observed that the transgenic misexpression of cxcr5 in the ventricular cells using dominant negative and full-length variants of the gene resulted in reduced and increased proliferation and neurogenesis response of the radial glial cell (RGC), respectively

  • We observed cxcr5 expression in a small number of cells close to the lesion site (Figure 1C, asterisk). These results indicate that cxcr5 is present in the adult zebrafish telencephalon during homeostasis, and its expression is significantly enhanced at the ventricular region after traumatic injury, suggesting that cxcr5 may be involved in adult neurogenesis and regenerative response of the telencephalon

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Summary

Introduction

Zebrafish exhibits extensive neural regeneration after injury in adult stages of its lifetime due to the neurogenic activity of the radial glial cells. The genes involved in the regenerative neurogenesis response of the zebrafish brain are largely unknown. The zebrafish has sixteen ventricular stem cell zones along the entire anterior-posterior brain axis [8]. One of these proliferation understanding the molecular basis of adult neurogenesis and brain regeneration in vertebrates. In order to identify genes involved in adult neurogenesis and regeneration response of the adult zebrafish telencephalon, we performed an in situ hybridization (ISH) screen. The ligand for cxcr is the B-cell-attracting chemokine 1 (BCA-1), known as Cxcl13 [20,21]. The role of cxcr gene in the adult neurogenesis and the regeneration of the central nervous system in vertebrates is unknown

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