Notch1 control of oligodendrocyte differentiation in the spinal cord.
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.
Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
Stephane
S
Genoud
Corinna
C
Lappe-Siefke
Sandra
S
Goebbels
Freddy
F
Radtke
Michel
M
Aguet
Steven S
SS
Scherer
Ueli
U
Suter
Klaus-Armin
KA
Nave
Ned
N
Mantei
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009836:Oligodendroglia / Q000502:physiology*; D016548:Prosencephalon / Q000502:physiology; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors
D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors