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Understanding the role of fezf2 in adult neural stem cell maintenance and fate: A study in zebrafish

  • Author(s): Berberoglu, Michael A.
  • Advisor(s): Guo, Su
  • Pleasure, Samuel
  • et al.
Abstract

Adult neurogenesis, or the birth of new neurons in the mature brain, is a process that occurs continuously and robustly from neural stem cells located in two discreet regions of the adult mammalian brain, the subventricular zone (SVZ) of the lateral ventricles, and the subgranular zone (SGZ) of the dentate gyrus region of the hippocampus. Though some progress has been made in understanding the factors which regulate the maintenance and fate of adult neural stem cells, our understanding remains limited. Fezf2, a conserved forebrain-specific transcription factor, is expressed during development in both zebrafish and mouse in regions where neural progenitor cells are present, and previous studies point to a role for Fezf2 in embryonic neurogenesis in both systems. Here, we show that fezf2 is expressed in the adult zebrafish forebrain, most notably in radial glial-like cells of the telencephalic ventricular zone, which label with markers of neural stem cells and proliferation. Further analysis using a fezf2-GFP transgenic zebrafish line indicates that these fezf2-expressing cells have neural stem cell-like properties, as they are able to self-renew and can likely give rise to glutamatergic neurons in the adult zebrafish telencephalon. Analysis of too few (Fezf2) homozygous mutant zebrafish crossed to our fezf2-GFP reporter line reveals a previously unreported adult telencephalic phenotype, including an increase in proliferation of fezf2-GFP+ cells, and an increase in adult neurogenesis. No major differences are observed in the mutant telencephalon at early larval stage, suggesting that the phenotype occurs largely at the late-larval to adult stage. Moreover, transplantation of fezf2-GFP+ mutant cells into wiltype hosts reveals a cell-autonomous role for fezf2 in maintaining the non-proliferative state of telencephalic radial glial cells. Taken together, our findings suggest a role for fezf2 in regulating the proliferation and differentiation of neural progenitor cells in the adult vertebrate telencephalon.

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