scholarly journals Severe Defects in Proliferation and Differentiation of Lens Cells in Foxe3 Null Mice

2005 ◽  
Vol 25 (20) ◽  
pp. 8854-8863 ◽  
Author(s):  
Olga Medina-Martinez ◽  
Isaac Brownell ◽  
Felipe Amaya-Manzanares ◽  
Qiyong Hu ◽  
Richard R. Behringer ◽  
...  
Keyword(s):  
Lens Epithelium ◽  
Abnormal Development ◽  
Distinct Region ◽  
Lens Development ◽  
Forkhead Transcription Factor ◽  
Surface Ectoderm ◽  
Dnase Ii ◽  
Lens Cells ◽  
Acid Dnase ◽  
Normal Lens

ABSTRACT During mouse eye development, the correct formation of the lens occurs as a result of reciprocal interactions between the neuroectoderm that forms the retina and surface ectoderm that forms the lens. Although many transcription factors required for early lens development have been identified, the mechanism and genetic interactions mediated by them remain poorly understood. Foxe3 encodes a winged helix-forkhead transcription factor that is initially expressed in the developing brain and in the lens placode and later restricted exclusively to the anterior lens epithelium. Here, we show that targeted disruption of Foxe3 results in abnormal development of the eye. Cells of the anterior lens epithelium show a decreased rate of proliferation, resulting in a smaller than normal lens. The anterior lens epithelium does not properly separate from the cornea and frequently forms an unusual, multilayered tissue. Because of the abnormal differentiation, lens fiber cells do not form properly, and the morphogenesis of the lens is greatly affected. The abnormally differentiated lens cells remain irregular in shape, and the lens becomes vacuolated. The defects in lens development correlate with changes in the expression of growth and differentiation factor genes, including DNase II-like acid DNase, Prox1, p57, and PDGFα receptor. As a result of abnormal lens development, the cornea and the retina are also affected. While Foxe3 is also expressed in a distinct region of the embryonic brain, we have not observed abnormal development of the brain in Foxe3 −/− animals.

The upstream ectoderm enhancer in Pax6 has an important role in lens induction

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4415-4424 ◽  
Author(s):  
Patricia V. Dimanlig ◽  
Sonya C. Faber ◽  
Woytek Auerbach ◽  
Helen P. Makarenkova ◽  
Richard A. Lang
Keyword(s):  
Transcriptional Control ◽  
Control Element ◽  
Pax6 Gene ◽  
Pax6 Expression ◽  
Surface Ectoderm ◽  
Targeted Deletion ◽  
Lens Vesicle ◽  
Normal Lens ◽  
Lens Formation ◽  
Lens Placode

The Pax6 gene has a central role in development of the eye. We show, through targeted deletion in the mouse, that an ectoderm enhancer in the Pax6 gene is required for normal lens formation. Ectoderm enhancer-deficient embryos exhibit distinctive defects at every stage of lens development. These include a thinner lens placode, reduced placodal cell proliferation, and a small lens pit and lens vesicle. In addition, the lens vesicle fails to separate from the surface ectoderm and the maturing lens is smaller and shows a delay in fiber cell differentiation. Interestingly, deletion of the ectoderm enhancer does not eliminate Pax6 production in the lens placode but results in a diminished level that, in central sections, is apparent primarily on the nasal side. This argues that Pax6 expression in the lens placode is controlled by the ectoderm enhancer and at least one other transcriptional control element. It also suggests that Pax6 enhancers active in the lens placode drive expression in distinct subdomains, an assertion that is supported by the expression pattern of a lacZ reporter transgene driven by the ectoderm enhancer. Interestingly, deletion of the ectoderm enhancer causes loss of expression of Foxe3, a transcription factor gene mutated in the dysgenetic lens mouse. When combined, these data and previously published work allow us to assemble a more complete genetic pathway describing lens induction. This pathway features (1) a pre-placodal phase of Pax6 expression that is required for the activity of multiple, downstream Pax6 enhancers; (2) a later, placodal phase of Pax6 expression regulated by multiple enhancers; and (3) the Foxe3 gene in a downstream position. This pathway forms a basis for future analysis of lens induction mechanism.

Clustered arrangement of winged helix genes fkh-6 and MFH-1: possible implications for mesoderm development

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1751-1758 ◽  
Author(s):  
K.H. Kaestner ◽  
S.C. Bleckmann ◽  
A.P. Monaghan ◽  
J. Schlondorff ◽  
A. Mincheva ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Chromosome 8 ◽  
Abnormal Development ◽  
Forkhead Transcription Factor ◽  
Winged Helix ◽  
Mesoderm Development ◽  
Physical Linkage ◽  
The Common ◽  
Somitic Mesoderm ◽  
Possible Cause

The ‘winged helix’ or ‘forkhead’ transcription factor gene family is defined by a common 100 amino acid DNA binding domain which is a variant of the helix-turn-helix motif. Here we describe the structure and expression of the mouse fkh-6 and MFH-1 genes. Both genes are expressed in embryonic mesoderm from the headfold stage onward. Transcripts for both genes are localised mainly to mesenchymal tissues, fkh-6 mRNA is enriched in the mesenchyme of the gut, lung, tongue and head, whereas MFH-1 is expressed in somitic mesoderm, in the endocardium and blood vessels as well as the condensing mesenchyme of the bones and kidney and in head mesenchyme. Both genes are located within a 10 kb region (in mouse chromosome 8 at 5.26 +/− 2.56 cM telomeric to Actsk1. The close physical linkage of these two winged helix genes is conserved in man, where the two genes map to chromosome 16q22-24. This tandem arrangement suggests the common use of regulatory mechanisms. The fkh-6/MFH-1 locus maps close to the mouse mutation amputated, which is characterised by abnormal development of somitic and facial mesoderm. Based on the expression patterns we suggest that a mutation in MFH-1, not fkh-6 is the possible cause for the amputated phenotype.

Drosophila acid DNase is a homolog of mammalian DNase II

Gene ◽  
2002 ◽  
Vol 295 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Cory J. Evans ◽  
John R. Merriam ◽  
Renato J. Aguilera
Keyword(s):  
Dnase Ii ◽  
Acid Dnase

scholarly journals Degradation of nuclear DNA by DNase II-like acid DNase in cortical fiber cells of mouse eye lens

FEBS Journal ◽  
2007 ◽  
Vol 274 (12) ◽  
pp. 3055-3064 ◽  
Author(s):  
Masaki Nakahara ◽  
Akiomi Nagasaka ◽  
Masato Koike ◽  
Kaori Uchida ◽  
Kohki Kawane ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Eye Lens ◽  
Dnase Ii ◽  
Fiber Cells ◽  
Acid Dnase

scholarly journals Forkhead transcription factor Foxf2 (LUN)-deficient mice exhibit abnormal development of secondary palate

2003 ◽  
Vol 259 (1) ◽  
pp. 83-94 ◽  
Author(s):  
Tao Wang ◽  
Tomoki Tamakoshi ◽  
Tadayoshi Uezato ◽  
Fang Shu ◽  
Naoko Kanzaki-Kato ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Abnormal Development ◽  
Forkhead Transcription Factor ◽  
Secondary Palate ◽  
Deficient Mice

The influence of Lyn kinase on Na,K-ATPase in porcine lens epithelium

2004 ◽  
Vol 286 (1) ◽  
pp. C90-C96 ◽  
Author(s):  
Larry D. Bozulic ◽  
William L. Dean ◽  
Nicholas A. Delamere
Keyword(s):  
Atpase Activity ◽  
Western Blot ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Tyrosine Phosphatase ◽  
Lens Epithelium ◽  
Membrane Material ◽  
Lyn Kinase ◽  
Multiple Protein ◽  
Lens Cells

Na,K-ATPase is essential for the regulation of cytoplasmic Na+and K+levels in lens cells. Studies on the intact lens suggest activation of tyrosine kinases may inhibit Na,K-ATPase function. Here, we tested the influence of Lyn kinase, a Src-family member, on tyrosine phosphorylation and Na,K-ATPase activity in membrane material isolated from porcine lens epithelium. Western blot studies indicated the expression of Lyn in lens cells. When membrane material was incubated in ATP-containing solution containing partially purified Lyn kinase, Na,K-ATPase activity was reduced by ∼38%. Lyn caused tyrosine phosphorylation of multiple protein bands. Immunoprecipitation and Western blot analysis showed Lyn treatment causes an increase in density of a 100-kDa phosphotyrosine band immunopositive for Na,K-ATPase α1polypeptide. Incubation with protein tyrosine phosphatase 1B (PTP-1B) reversed the Lyn-dependent tyrosine phosphorylation increase and the change of Na,K-ATPase activity. The results suggest that Lyn kinase treatment of a lens epithelium membrane preparation is able to bring about partial inhibition of Na,K-ATPase activity associated with tyrosine phosphorylation of multiple membrane proteins, including the Na,K-ATPase α1catalytic subunit.

scholarly journals The heat-inducible zebrafish hsp70 gene is expressed during normal lens development under non-stress conditions

2002 ◽  
Vol 112 (1-2) ◽  
pp. 213-215 ◽  
Author(s):  
Scott R. Blechinger ◽  
Tyler G. Evans ◽  
Ping Tao Tang ◽  
John Y. Kuwada ◽  
James T. Warren ◽  
...  
Keyword(s):  
Stress Conditions ◽  
Hsp70 Gene ◽  
Lens Development ◽  
Normal Lens

scholarly journals Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells

2015 ◽  
Vol 26 (13) ◽  
pp. 2561-2572 ◽  
Author(s):  
Bruce A. Boswell ◽  
Linda S. Musil
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Bone Morphogenetic Protein ◽  
Primary Cultures ◽  
Bmp Signaling ◽  
Fibroblast Growth ◽  
Lens Development ◽  
Morphogenetic Protein ◽  
Lens Cells ◽  
And Function

Fibroblast growth factors (FGFs) play a central role in two processes essential for lens transparency—fiber cell differentiation and gap junction–mediated intercellular communication (GJIC). Using serum-free primary cultures of chick lens epithelial cells (DCDMLs), we investigated how the FGF and bone morphogenetic protein (BMP) signaling pathways positively cooperate to regulate lens development and function. We found that culturing DCDMLs for 6 d with the BMP blocker noggin inhibits the canonical FGF-to-ERK pathway upstream of FRS2 activation and also prevents FGF from stimulating FRS2- and ERK-independent gene expression, indicating that BMP signaling is required at the level of FGF receptors. Other experiments revealed a second type of BMP/FGF interaction by which FGF promotes expression of BMP target genes as well as of BMP4. Together these studies reveal a novel mode of cooperation between the FGF and BMP pathways in which BMP keeps lens cells in an optimally FGF-responsive state and, reciprocally, FGF enhances BMP-mediated gene expression. This interaction provides a mechanistic explanation for why disruption of either FGF or BMP signaling in the lens leads to defects in lens development and function.

Ontogeny and localization of the crystallins during lens development normal and Hy-1 (hyperplastic lens epithelium) chick embryos

Development ◽  
1979 ◽  
Vol 50 (1) ◽  
pp. 31-45
Author(s):  
David S. McDevitt ◽  
Ruth M. Clayton
Keyword(s):  
Growth Regulation ◽  
High Growth ◽  
High Growth Rate ◽  
Fiber Formation ◽  
Lens Epithelium ◽  
Specific Gene ◽  
External Layer ◽  
Lens Crystallins ◽  
Organ Specific ◽  
Normal Lens

A strain of chickens selected for high growth rate has been found to exhibit an anomalous eye lens morphology indicating a failure of the normal process of growth regulation. Hyperplasia of the lens epithelium and annular pad, often with fiber formation, has recently been described in day-old chicks of this strain, termed Hy-1 (Clayton, 1975). The earliest evidence of this condition in this study has been found in the 11-day embryonic Hy-1 lens. Before this time, no definitive lens abnormality could be detected histologically in the Hy-1 embryos.However, the indirect immunofiuorescence technique had revealed early temporal and spatial differences with regard to the lens crystallins. Antibodies, specific for δ, cathodal β, anodal β and α crystallins, were applied to sections through the lens of 2½-, 3-, 3½-, 4-, 5-, 8- and 16-day embryonic and 1-day post-hatch normal and Hy-1 chicks. δ crystallin appears precociously in the external layer, and α crystallin in the prospective fiber region, of the lens rudiment of Hy-1 embryos. Both anodal and cathodal β crystallins are retarded, however, in their appearance in the external layer/epithelium of Hy-1 lenses. Localization of the crystallin classes within the lenses of the two strains continues to vary during lens differentiation until 1 day post-hatch, at which time and during late embryogenesis annular pad and epithelium abnormalities can be frequently be seen in the Hy-1 lens. This inability to control normal lens histogenesis thus manifests itself early as alterations in the appearance of an organ-specific gene product, the crystallins.

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