Analysis of the molecular mechanisms regulating the maintenance of multipotency and the dedifferentiation of neural stem cells

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To shed light on the temporal and regional differences of embryonic neural stem cells, we sorted the green fluorescent protein (GFP)-positive neural stem cells from the telencephalon of pHes1-d2EGFP transgenic mouse embryos at different developmental stages, and from different regions of the telencephalon of the transgenic mice at embryonic day 11.5, and performed gene expression profiling. Among dozens of transcription factors differentially expressed by cells in the ventricular zone during the course of development, several of them exhibited the activity to inhibit neuronal differentiation when overexpressed. Furthermore, knock-down of Tcf3 or Klf15 led to accelerated neuronal differentiation, suggesting that these transcription factors play critical roles in the maintenance of neural stem cells at early and late embryonic stages, respectively.