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The Journal of Neuroscience, March 5, 2008, 28(10):2551-2562; doi:10.1523/JNEUROSCI.5497-07.2008

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Development/Plasticity/Repair
Early Neuronal and Glial Fate Restriction of Embryonic Neural Stem Cells

Delphine Delaunay,^1,2 Katharina Heydon,^1,2 Ana Cumano,³ Markus H. Schwab,⁴ Jean-Léon Thomas,^1,2 Ueli Suter,⁵ Klaus-Armin Nave,⁴ Bernard Zalc,^1,2 and Nathalie Spassky^1,2

¹Inserm, Unité 711, 75013 Paris, France, ²Institut Fédératif de Recherche 70, Faculté de Médecine, Université Pierre et Marie Curie, 75013 Paris, France, ³Inserm, Unité 668, Institut Pasteur, 75724 Paris Cedex 15, France, ⁴Max-Planck-Institute of Experimental Medicine, D-37075 Goettingen, Germany, and ⁵Institute of Cell Biology, Swiss Federal Institute of Technology (ETH), ETH Hönggerberg, CH-8093 Zürich, Switzerland

Correspondence should be addressed to B. Zalc, Biologie des Interactions Neurones/Glie, Inserm Unité 711, Université Pierre et Marie Curie, Hôpital de la Salpêtrière 75651 Paris cedex 13, France. Email: berzalc{at}ccr.jussieu.fr

The question of how neurons and glial cells are generated during the development of the CNS has over time led to two alternative models: either neuroepithelial cells are capable of giving rise to neurons first and to glial cells at a later stage (switching model), or they are intrinsically committed to generate one or the other (segregating model). Using the developing diencephalon as a model and by selecting a subpopulation of ventricular cells, we analyzed both in vitro, using clonal analysis, and in vivo, using inducible Cre/loxP fate mapping, the fate of neuroepithelial and radial glial cells generated at different time points during embryonic development. We found that, during neurogenic periods [embryonic day 9.5 (E9.5) to 12.5], proteolipid protein (plp)-expressing cells were lineage-restricted neuronal precursors, but later in embryogenesis, during gliogenic periods (E13.5 to early postnatal), plp-expressing cells were lineage-restricted glial precursors. In addition, we show that glial cells forming at E13.5 arise from a new pool of neuroepithelial progenitors distinct from neuronal progenitors cells, which lends support to the segregating model.

Key words: diencephalon; plp; mouse; in vivo genetic fate mapping; neuroblast; glioblast

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Received Feb. 4, 2007; accepted Jan. 14, 2008.

Correspondence should be addressed to B. Zalc, Biologie des Interactions Neurones/Glie, Inserm Unité 711, Université Pierre et Marie Curie, Hôpital de la Salpêtrière 75651 Paris cedex 13, France. Email: berzalc{at}ccr.jussieu.fr

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