Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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Biomarkers
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Cell Differentiation*
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Cell Survival
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Cells, Cultured
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Cerebellum / cytology*
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Cerebellum / embryology*
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Cerebellum / growth & development
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Cerebellum / physiology
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Embryo, Mammalian / anatomy & histology
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Embryo, Mammalian / physiology
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Gene Expression Regulation, Developmental
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Genes, Reporter
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Immunohistochemistry
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In Situ Hybridization
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In Situ Nick-End Labeling
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Integrases / genetics
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Integrases / metabolism
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Intermediate Filament Proteins / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Transgenic
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Nerve Tissue Proteins*
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Nestin
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Neuroglia / cytology*
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Neuroglia / physiology
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Neurons / cytology*
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Neurons / physiology
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Receptor, Notch1
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Receptors, Cell Surface*
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Signal Transduction
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Transcription Factors*
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Viral Proteins / genetics
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Viral Proteins / metabolism
Substances
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Biomarkers
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Intermediate Filament Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Nes protein, mouse
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Nestin
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Notch1 protein, mouse
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Receptor, Notch1
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Receptors, Cell Surface
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Transcription Factors
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Viral Proteins
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Cre recombinase
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Integrases