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Notch1 is required for neuronal and glial differentiation in the cerebellum

Simone Lütolf^1,*, Freddy Radtke^2,*, Michel Aguet², Ueli Suter¹ and Verdon Taylor^1,

¹ Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland
² Swiss Institute of Experimental Cancer Research, 1066 Epalinges, Switzerland
^* These authors contributed equally to this work

Author for correspondence (e-mail: taylor{at}cell.biol.ethz.ch)

Accepted 24 October 2001

The mechanisms that guide progenitor cell fate and differentiation in the vertebrate central nervous system (CNS) are poorly understood. Gain-of-function experiments suggest that Notch signaling is involved in the early stages of mammalian neurogenesis. On the basis of the expression of Notch1 by putative progenitor cells of the vertebrate CNS, we have addressed directly the role of Notch1 in the development of the mammalian brain. Using conditional gene ablation, we show that loss of Notch1 results in premature onset of neurogenesis by neuroepithelial cells of the midbrain-hindbrain region of the neural tube. Notch1-deficient cells do not complete differentiation but are eliminated by apoptosis, resulting in a reduced number of neurons in the adult cerebellum. We have also analyzed the effects of Notch1 ablation on gliogenesis in vivo. Our results show that Notch1 is required for both neuron and glia formation and modulates the onset of neurogenesis within the cerebellar neuroepithelium.

Key words: Notch, Neurogenesis, CNS, Cerebellum, Apoptosis, Mouse

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