Abstract
We have investigated the role of the cyclin-dependent kinase inhibitor, p27(Xic1), in the coordination of cell cycle exit and differentiation during early neurogenesis. We demonstrate that p27(Xic1) is highly expressed in cells destined to become primary neurones and is essential for an early stage of neurogenesis. Ablation of p27(Xic1) protein prevents differentiation of primary neurones, while overexpressing p27(Xic1) promotes their formation. p27(Xic1) may enhance neurogenesis by stabilising the bHLH protein, neurogenin. Moreover, the ability of p27(Xic1) to stabilise neurogenin and enhance neurogenesis localises to an N-terminal domain of the molecule and is separable from its ability to inhibit the cell cycle.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Differentiation
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Embryo, Nonmammalian
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Embryonic Induction / physiology*
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Gene Expression Regulation, Developmental
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / cytology*
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Neurons / physiology
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Xenopus Proteins / genetics
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Xenopus Proteins / metabolism*
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Xenopus laevis / embryology*
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Xenopus laevis / genetics
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Cell Cycle Proteins
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Nerve Tissue Proteins
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Tumor Suppressor Proteins
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Xenopus Proteins
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Xicl protein, Xenopus
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neurogenin, Xenopus
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Cyclin-Dependent Kinase Inhibitor p27
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Neurogenic differentiation factor 1
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Cyclin-Dependent Kinases