PUBLICATION

The chemokine receptor cxcr5 regulates the regenerative neurogenesis response in the adult zebrafish brain

Authors
Kizil, C., Dudczig, S., Kyritsis, N., Machate, A., Blaesche, J., Kroehne, V., and Brand, M.
ID
ZDB-PUB-120725-2
Date
2012
Source
Neural Development   7(1): 27 (Journal)
Registered Authors
Brand, Michael, Dudczig, Stefanie, Kizil, Caghan, Kroehne, Volker, Kyritsis, Nikos, Machate, Anja
Keywords
none
MeSH Terms
  • Animals
  • Brain/metabolism*
  • Cell Proliferation
  • Nerve Regeneration/physiology*
  • Neurogenesis/physiology*
  • Neuroglia/metabolism
  • Neurons/metabolism
  • Receptors, CXCR5/genetics
  • Receptors, CXCR5/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
22824261 Full text @ Neural Dev.
Abstract

Background

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. 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 zebrafish brain is an interesting research realm that may offer vast clinical ramifications.

Results

In 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 is upregulated transiently in the RGCs and neurons, and the expression in the immune cells such as leukocytes is 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.

Conclusions

Thus, 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.

Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping