Prox1 function is crucial for mouse lens-fibre elongation

• Published in: Nature genetics Vol. 21; no. 3; pp. 318 - 322
• Main Authors: Oliver, Guillermo, Wigle, Jeffrey T, Chowdhury, Kamal, Gruss, Peter
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.03.1999
• Subjects: Animals; beta-Galactosidase - genetics; Biological and medical sciences; Bromodeoxyuridine - analysis; Bromodeoxyuridine - metabolism; Cell Cycle Proteins; Cell Differentiation - genetics; Cell Division - genetics; Classical genetics, quantitative genetics, hybrids; Crystallins - genetics; Cyclin-Dependent Kinase Inhibitor p27; Embryonic Induction - genetics; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression Regulation, Developmental; Genetics of eukaryotes. Biological and molecular evolution; 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; Vertebrata; Embryonic development; Vertebrata; Mammalia; Mouse; Rodentia; Lens; Mutation; Cell differentiation; Gene expression; Elongation
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/6844

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.