Abstract
The Notch signalling pathway plays a crucial role in specifying cellular fates in metazoan development by regulating communication between adjacent cells. Correlative studies suggested an involvement of Notch in intestinal development. Here, by modulating Notch activity in the mouse intestine, we directly implicate Notch signals in intestinal cell lineage specification. We also show that Notch activation is capable of amplifying the intestinal progenitor pool while inhibiting cell differentiation. We conclude that Notch activity is required for the maintenance of proliferating crypt cells in the intestinal epithelium.
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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Apoptosis
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Basic Helix-Loop-Helix Transcription Factors
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Cell Differentiation
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Cell Lineage*
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Cell Proliferation
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DNA-Binding Proteins / genetics
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Epithelial Cells / cytology
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Epithelial Cells / metabolism
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Female
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Gene Expression Regulation
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Integrases / genetics
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Integrases / metabolism
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Intestinal Mucosa / metabolism*
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Intestines / cytology*
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Male
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Mice
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Mice, Transgenic
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Nerve Tissue Proteins / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, Notch1
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Signal Transduction*
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Stem Cells / cytology*
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Stem Cells / metabolism*
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Transcription Factor HES-1
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Viral Proteins / genetics
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Viral Proteins / metabolism
Substances
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Atoh1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Hes1 protein, mouse
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Homeodomain Proteins
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Nerve Tissue Proteins
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Neurog3 protein, mouse
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Notch1 protein, mouse
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RNA, Messenger
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Receptor, Notch1
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Receptors, Cell Surface
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Transcription Factor HES-1
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Transcription Factors
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Viral Proteins
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Cre recombinase
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Integrases