Abstract
Although insights have emerged regarding genes controlling the early stages of eye formation, little is known about lens-fibre differentiation and elongation. The expression pattern of the Prox1 homeobox gene suggests it has a role in a variety of embryonic tissues, including lens. To analyse the requirement for Prox1 during mammalian development, we inactivated the locus in mice. Homozygous Prox1-null mice die at mid-gestation from multiple developmental defects; here we describe the specific effect on lens development. Prox1 inactivation causes abnormal cellular proliferation, downregulated expression of the cell-cycle inhibitors Cdkn1b (also known as p27KIP1) and Cdkn1c (also known as p57KIP2), misexpression of E-cadherin and inappropriate apoptosis. Consequently, mutant lens cells fail to polarize and elongate properly, resulting in a hollow lens. Our data provide evidence that the progression of terminal fibre differentiation and elongation is dependent on Prox1 activity during lens development.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bromodeoxyuridine / analysis
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Bromodeoxyuridine / metabolism
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Cell Cycle Proteins*
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Cell Differentiation / genetics
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Cell Division / genetics
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Crystallins / genetics
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Cyclin-Dependent Kinase Inhibitor p27
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Embryonic Induction / genetics
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Gene Expression Regulation, Developmental*
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / physiology
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Immunohistochemistry
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Lens, Crystalline / abnormalities
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Lens, Crystalline / cytology*
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Lens, Crystalline / embryology*
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Mice
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Mice, Mutant Strains
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Molecular Motor Proteins
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Mutation
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Saccharomyces cerevisiae Proteins*
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Tumor Suppressor Proteins*
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beta-Galactosidase / genetics
Substances
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Cdkn1b protein, mouse
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Cell Cycle Proteins
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Crystallins
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Fungal Proteins
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Homeodomain Proteins
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KIP2 protein, S cerevisiae
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Microtubule-Associated Proteins
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Molecular Motor Proteins
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Saccharomyces cerevisiae Proteins
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Tumor Suppressor Proteins
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prospero-related homeobox 1 protein
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Cyclin-Dependent Kinase Inhibitor p27
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beta-Galactosidase
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Bromodeoxyuridine