PT - JOURNAL ARTICLE AU - Michael A. Berberoglu AU - Zhiqiang Dong AU - Guangnan Li AU - Jiashun Zheng AU - Luz del Carmen G. Trejo Martinez AU - Jisong Peng AU - Mahendra Wagle AU - Brian Reichholf AU - Claudia Petritsch AU - Hao Li AU - Samuel J. Pleasure AU - Su Guo TI - Heterogeneously Expressed <em>fezf2</em> Patterns Gradient Notch Activity in Balancing the Quiescence, Proliferation, and Differentiation of Adult Neural Stem Cells AID - 10.1523/JNEUROSCI.1976-14.2014 DP - 2014 Oct 15 TA - The Journal of Neuroscience PG - 13911--13923 VI - 34 IP - 42 4099 - http://www.jneurosci.org/content/34/42/13911.short 4100 - http://www.jneurosci.org/content/34/42/13911.full SO - J. Neurosci.2014 Oct 15; 34 AB - 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-GFPhi quiescent and fezf2-GFPlo 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-GFPhi quiescent and fezf2-GFPlo 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.