Nuclear Notch1 signaling and the regulation of dendritic development.
To understand the function of Notch in the mammalian brain, we examined Notch1 signaling and its cellular consequences in developing cortical neurons. We found that the cytoplasmic domain of endogenous Notch1 translocated to the nucleus during neuronal differentiation. Notch1 cytoplasmic-domain constructs transfected into cortical neurons were present in multiple phosphorylated forms, localized to the nucleus and could induce CBF1-mediated transactivation. Molecular perturbation experiments suggested that Notch1 signaling in cortical neurons promoted dendritic branching and inhibited dendritic growth. These observations show that Notch1 signaling to the nucleus exerts an important regulatory influence on the specification of dendritic morphology in neurons.
Redmond
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Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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Hicks
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Weinmaster
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Ghosh
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D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development; D003712:Dendrites / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D020318:Rats, Long-Evans; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D014162:Transfection
D008565:Membrane Proteins; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D001973:Bromodeoxyuridine