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PMID:10080188
| Citation |
Wigle, JT, Chowdhury, K, Gruss, P and Oliver, G (1999) Prox1 function is crucial for mouse lens-fibre elongation. Nat. Genet. 21:318-22 |
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| 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. |
| Links |
PubMed Online version:10.1038/6844 |
| Keywords |
Animals; Bromodeoxyuridine/analysis; Bromodeoxyuridine/metabolism; Cell Cycle Proteins; Cell Differentiation/genetics; Cell Division/genetics; Crystallins/genetics; Cyclin-Dependent Kinase Inhibitor p27; Embryonic Induction/genetics; Fungal Proteins/genetics; Fungal Proteins/metabolism; Gene Expression Regulation, Developmental; Homeodomain Proteins/genetics; Homeodomain Proteins/physiology; Immunohistochemistry; Lens, Crystalline/abnormalities; Lens, Crystalline/cytology; Lens, Crystalline/embryology; Mice; Mice, Mutant Strains; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Molecular Motor Proteins; Mutation; Saccharomyces cerevisiae Proteins; Tumor Suppressor Proteins; beta-Galactosidase/genetics |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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