Stem Cells
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First published online April 20, 2006
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2006-0031v1
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Submitted on January 17, 2006
Accepted on April 12, 2006

Embryonic Stem Cells

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

Isabelle A. Bouhon 1, Alexis Joannides 2, Hidemasa Kato 1, Siddharthan Chandran 2, Nicholas D. Allen 3*

1 Neurobiology Programme, The Babraham Institute, Babraham, Cambridge, United Kingdom
2 Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom
3 School of Biosciences, Cardiff University, Cardiff, United Kingdom

* To whom correspondence should be addressed. E-mail: allennd{at}cf.ac.uk.


  Abstract

Neural stem cells have considerable therapeutic potential on account 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 ES derived neural progenitors is temporally restricted and show that the loss of responsiveness to morphogenetic cues correlates with constitutive expression of the bHLH transcription factors Olig2 and Mash1, EGFR 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.

Key Words. embryonic stem cell, neural differentiation, patterning, temporal restriction, radial glia




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