ZFIN ID: ZDB-PUB-141018-8
Heterogeneously Expressed fezf2 Patterns Gradient Notch Activity in Balancing the Quiescence, Proliferation, and Differentiation of Adult Neural Stem Cells
Berberoglu, M.A., Dong, Z., Li, G., Zheng, J., Trejo Martinez, L.d.e.l. .C., Peng, J., Wagle, M., Reichholf, B., Petritsch, C., Li, H., Pleasure, S.J., Guo, S.
Date: 2014
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience   34: 13911-23 (Journal)
Registered Authors: Berberoglu, Michael, Dong, Zhiqiang, Guo, Su, Peng, Jisong, Wagle, Mahendra
Keywords: adult neurogenesis, hippocampus, radial glia, self-renewal, single-cell analysis, vivo morpholino
MeSH Terms:
  • Adult Stem Cells/metabolism*
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/physiology*
  • Cell Proliferation/physiology*
  • DNA-Binding Proteins/biosynthesis*
  • Female
  • Gene Expression Regulation, Developmental
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins/biosynthesis*
  • Neural Stem Cells/metabolism*
  • Neurogenesis/physiology
  • Receptors, Notch/metabolism*
  • Zebrafish
PubMed: 25319688 Full text @ J. Neurosci.
Balancing quiescence, self-renewal, and differentiation in adult stem cells is critical for tissue homeostasis. The underlying mechanisms, however, remain incompletely understood. Here we identify Fezf2 as a novel regulator of fate balance in adult zebrafish dorsal telencephalic neural stem cells (NSCs). Transgenic reporters show intermingled fezf2-GFP(hi) quiescent and fezf2-GFP(lo) proliferative NSCs. Constitutive or conditional impairment of fezf2 activity demonstrates its requirement for maintaining quiescence. Analyses of genetic chimeras reveal a dose-dependent role of fezf2 in NSC activation, suggesting that the difference in fezf2 levels directionally biases fate. Single NSC profiling coupled with genetic analysis further uncovers a fezf2-dependent gradient Notch activity that is high in quiescent and low in proliferative NSCs. Finally, fezf2-GFP(hi) quiescent and fezf2-GFP(lo) proliferative NSCs are observed in postnatal mouse hippocampus, suggesting possible evolutionary conservation. Our results support a model in which fezf2 heterogeneity patterns gradient Notch activity among neighbors that is critical to balance NSC fate.