We have selectively inhibited Notch1 signaling in oligodendrocyte precursors (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of Notch1 in oligodendrocyte (OL) development and differentiation. Early development of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5, premature OL differentiation was observed and ectopic immature OLs were present in the gray matter. At birth, OL apoptosis was strongly increased in Notch1 mutant animals. Premature OL differentiation was also observed in the cerebrum, indicating that Notch1 is required for the correct spatial and temporal regulation of OL differentiation in various regions of the central nervous system. These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo.
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19 August 2002
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August 19 2002
Notch1 control of oligodendrocyte differentiation in the spinal cord
Stéphane Genoud,
Stéphane Genoud
1Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland
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Corinna Lappe-Siefke,
Corinna Lappe-Siefke
2Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, D-37075 Göttingen, Germany
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Sandra Goebbels,
Sandra Goebbels
2Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, D-37075 Göttingen, Germany
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Freddy Radtke,
Freddy Radtke
3Swiss Institute of Experimental Cancer Research, CH-1066 Epalinges, Switzerland
4Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland
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Michel Aguet,
Michel Aguet
3Swiss Institute of Experimental Cancer Research, CH-1066 Epalinges, Switzerland
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Steven S. Scherer,
Steven S. Scherer
5Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, PA 19104
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Ueli Suter,
Ueli Suter
1Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland
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Klaus-Armin Nave,
Klaus-Armin Nave
2Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, D-37075 Göttingen, Germany
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Ned Mantei
Ned Mantei
1Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland
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Stéphane Genoud
1Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland
Corinna Lappe-Siefke
2Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, D-37075 Göttingen, Germany
Sandra Goebbels
2Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, D-37075 Göttingen, Germany
Freddy Radtke
3Swiss Institute of Experimental Cancer Research, CH-1066 Epalinges, Switzerland
4Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland
Michel Aguet
3Swiss Institute of Experimental Cancer Research, CH-1066 Epalinges, Switzerland
Steven S. Scherer
5Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, PA 19104
Ueli Suter
1Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland
Klaus-Armin Nave
2Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, D-37075 Göttingen, Germany
Ned Mantei
1Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland
Address correspondence to Ned Mantei, Institute of Cell Biology, Dept. of Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland. Tel.: 41-1-633-3685. Fax: 41-1-633-1190. E-mail: [email protected]
*
Abbreviations used in this paper: β-gal, β-galactosidase; CNP, 2′,3′-cyclic nucleotide 3′-phosphodiesterase; CNS, central nervous system; GFAP, glial fibrillary acidic protein; MAG, myelin-associated glycoprotein; MBP, myelin basic protein; NeuN, neuronal nuclear antigen; OPC, oligodendrocyte precursor cell; OL, oligodendrocyte; PDGFR-α, PDGF receptor α; Plp, proteolipid protein.
Received:
February 01 2002
Revision Received:
July 15 2002
Accepted:
July 15 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 158 (4): 709–718.
Article history
Received:
February 01 2002
Revision Received:
July 15 2002
Accepted:
July 15 2002
Citation
Stéphane Genoud, Corinna Lappe-Siefke, Sandra Goebbels, Freddy Radtke, Michel Aguet, Steven S. Scherer, Ueli Suter, Klaus-Armin Nave, Ned Mantei; Notch1 control of oligodendrocyte differentiation in the spinal cord . J Cell Biol 19 August 2002; 158 (4): 709–718. doi: https://doi.org/10.1083/jcb.200202002
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