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EMBRYONIC STEM CELLS

Embryonic Stem Cell-Derived Neural Progenitors Display Temporal Restriction to Neural Patterning

^aNeurobiology Programme, The Babraham Institute, Babraham, Cambridge, United Kingdom;
^bCambridge Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom;
^cSchool of Biosciences, Cardiff University, Cardiff, United Kingdom

Key Words. Embryonic stem cell • Neural differentiation • Patterning • Temporal restriction • Radial glia

Correspondence: Nicholas D. Allen, Ph.D., School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3US, U.K. Telephone: +44 29 2087 6196; Fax: +44 29 2087 6328; e-mail: allennd{at}cf.ac.uk or Siddharthan Chandran, MRCP Ph.D., Cambridge Centre for Brain Repair, University of Cambridge, Cambridge CB2 2PY, U.K., Telephone: +44 1223331160; Fax: +44 1223331174; e-mail: sc222{at}cam.ac.uk

Received January 17, 2006; accepted for publication April 12, 2006.
First published online in STEM CELLS EXPRESS   April 20, 2006.



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.

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