Embryonic stem cell-derived neural progenitors display temporal restriction to neural patterning

Neural stem cells have considerable therapeutic potential because of their ability to generate defined neuronal cell types for use in drug screening studies or cell-based therapies for neurodegenerative diseases. In this study, we differentiate mouse embryonic stem cells to neural progenitors with an initial forebrain identity in a defined system that enables systematic manipulation to generate more caudal fates, including motoneurons. We demonstrate that the ability to pattern embryonic stem cell-derived neural progenitors is temporally restricted and show that the loss of responsiveness to morphogenetic cues correlates with constitutive expression of the basic helix-loop-helix transcription factors Olig2 and Mash1, epidermal growth factor receptor, and vimentin and parallels the onset of gliogenesis. We provide evidence for two temporal classes of embryonic stem cell-derived putative radial glia that coincide with a transition from neurogenesis to gliogenesis and a concomitant loss of regional identity.