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doi: 10.1242/10.1242/dev.00374
1 Laboratoire de Neurobiologie du Développement et de la
Régénération — CNRS, 5 rue Blaise Pascal, 67000
Strasbourg, France
2 Department of Anatomy and Neurobiology, College of Medicine, University of
Vermont, Burlington, VT 05405, USA
3 GSF, Institute for Mammalian Genetics, Ingolstaedter Landstrasse 1, D-85764
Neuherberg, Germany
4 Massachusetts General Hospital Cancer Center, Department of Cell Biology,
Harvard Medical School, Charlestown, Massachusetts 02129, USA
5 Laboratoire d'embryologie cellulaire et moléculaire —
Collège de France, 49B, Avenue de la Belle Gabrielle, 94736 Nogent sur
Marne, France
* Author for correspondence (e-mail: mohier{at}neurochem.u-strasbg.fr)
Accepted 10 December 2002
We examined the role of Notch signaling on the generation of neurons and glia from neural stem cells by using neurospheres that are clonally derived from neural stem cells. Neurospheres prepared from Dll1lacZ/lacZ mutant embryos segregate more neurons at the expense of both oligodendrocytes and astrocytes. This mutant phenotype could be rescued when Dll1lacZ/lacZ spheres were grown and/or differentiated in the presence of conditioned medium from wild-type neurospheres. Temporal modulation of Notch by soluble forms of ligands indicates that Notch signaling acts in two steps. Initially, it inhibits the neuronal fate while promoting the glial cell fate. In a second step, Notch promotes the differentiation of astrocytes, while inhibiting the differentiation of both neurons and oligodendrocytes.
Key words: Neural stem cells, Notch-Delta signaling, Cell fate specification, Neurospheres, Mouse
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