Abstract
The size of an organ must be tightly controlled so that it fits within an organism. The mammalian lens is a relatively simple organ composed of terminally differentiated, amitotic lens fiber cells capped on the anterior surface by a layer of immature, mitotic epithelial cells. The proliferation of lens epithelial cells fuels the growth of the lens, thus controling the size of the lens. We report that the Notch signaling pathway defines the boundary between proliferation and differentiation in the developing lens. The loss of Notch signaling results in the loss of epithelial cells to differentiation and a much smaller lens. We found that the Notch effector Herp2 is expressed in lens epithelium and directly suppresses p57Kip2 expression, providing a molecular link between Notch signaling and the cell cycle control machinery during lens development.
Publication types
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Research Support, N.I.H., Extramural
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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 Leucine Zipper Transcription Factors / genetics
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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COS Cells
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Cell Cycle / physiology
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Cell Differentiation / physiology
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Cell Proliferation
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Chlorocebus aethiops
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Cyclin-Dependent Kinase Inhibitor p57 / genetics
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Cyclin-Dependent Kinase Inhibitor p57 / metabolism*
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Epithelial Cells / cytology
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Epithelial Cells / physiology
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Gene Expression Regulation*
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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In Situ Hybridization
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Lens, Crystalline* / anatomy & histology
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Lens, Crystalline* / physiology
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Mice
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Mice, Knockout
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Phenotype
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Receptors, Notch / genetics
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Receptors, Notch / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Signal Transduction / physiology*
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic Helix-Loop-Helix Transcription Factors
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Cyclin-Dependent Kinase Inhibitor p57
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Hey2 protein, mouse
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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Rbpj protein, mouse
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Receptors, Notch
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Repressor Proteins