Abstract
Regulation of self-renewal and differentiation of neural stem cells is still poorly understood. Here we investigate the role of a developmentally expressed protein, Botch, which blocks Notch, in neocortical development. Downregulation of Botch in vivo leads to cellular retention in the ventricular and subventricular zones, whereas overexpression of Botch drives neural stem cells into the intermediate zone and cortical plate. In vitro neurosphere and differentiation assays indicate that Botch regulates neurogenesis by promoting neuronal differentiation. Botch prevents cell surface presentation of Notch by inhibiting the S1 furin-like cleavage of Notch, maintaining Notch in the immature full-length form. Understanding the function of Botch expands our knowledge regarding both the regulation of Notch signaling and the complex signaling mediating neuronal development.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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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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Blotting, Western
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Differentiation*
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Cell Membrane / metabolism
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Cells, Cultured
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Embryo, Mammalian / cytology
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Embryo, Mammalian / metabolism*
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Golgi Apparatus / metabolism
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Humans
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Immunoprecipitation
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Mice
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Neural Stem Cells / cytology*
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Neural Stem Cells / metabolism
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Neurogenesis / physiology*
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Neurons / cytology
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Neurons / metabolism
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Neuroprotective Agents / metabolism*
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Receptors, Notch / antagonists & inhibitors*
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Receptors, Notch / genetics
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Receptors, Notch / metabolism*
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Signal Transduction
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gamma-Glutamylcyclotransferase
Substances
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Carrier Proteins
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GGCT protein, human
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Neuroprotective Agents
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RNA, Messenger
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Receptors, Notch
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gamma-Glutamylcyclotransferase