Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pitx3 is a bicoid like homeobox transcription factor of which deficiency in mice is linked with the aphakia phenotype. Mutation in human PITX3 gene is associated with autosomal dominant cataract with variable anterior segment mesenchymal dysgenesis. However, the molecular events causing the morphological changes in aphakia remains unknown. In this study we investigated the behaviour of GFP tagged Pitx3 null embryonic stem cells in chimeric lens, as well as the molecular features of the Pitx3-deficient lens of homozygous Pitx3 knockout mice. We show that the lack of colonisation of Pitx3-deficient ES cell derivatives in Pitx3 wild-type<-->Pitx3 null chimeric lens was due to the depletion of the epithelial cells in lens epithelium manifested by aberrant cell cycle exit and precocious onset of fibre cell differentiation of the Pitx3 null cells at the lens vesicle stage. This was demonstrated by the early activation of the cell cycle inhibitors p27Kip1 and p57Kip2, and the expression of beta-and gamma-crystallins. These defects are at least partially attributed to the loss of FoxE3 and misexpression of Prox1 in the lens vesicle epithelial cells. Thus, Pitx3 is essential to maintain lens epithelial phenotype and prevent inappropriate fibre cell differentiation during lens development.
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PMID:Homeodomain protein Pitx3 maintains the mitotic activity of lens epithelial cells. 1900 84

Opacification of the ocular lens, termed cataract, is a common cause of blindness. To become transparent, lens fiber cells undergo degradation of their organelles, including their nuclei, presenting a fundamental question: does signaling/transcription sufficiently explain differentiation of cells progressing toward compromised transcriptional potential? We report that a conserved RNA-binding protein Celf1 post-transcriptionally controls key genes to regulate lens fiber cell differentiation. Celf1-targeted knockout mice and celf1-knockdown zebrafish and Xenopus morphants have severe eye defects/cataract. Celf1 spatiotemporally down-regulates the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 by interacting with its 5' UTR and mediating translation inhibition. Celf1 deficiency causes ectopic up-regulation of p21Cip1. Further, Celf1 directly binds to the mRNA of the nuclease Dnase2b to maintain its high levels. Together these events are necessary for Cdk1-mediated lamin A/C phosphorylation to initiate nuclear envelope breakdown and DNA degradation in fiber cells. Moreover, Celf1 controls alternative splicing of the membrane-organization factor beta-spectrin and regulates F-actin-crosslinking factor Actn2 mRNA levels, thereby controlling fiber cell morphology. Thus, we illustrate new Celf1-regulated molecular mechanisms in lens development, suggesting that post-transcriptional regulatory RNA-binding proteins have evolved conserved functions to control vertebrate oculogenesis.
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PMID:The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development. 2956 69