scholarly journals A forkhead gene, FoxE3, is essential for lens epithelial proliferation and closure of the lens vesicle

2000 ◽  
Vol 14 (2) ◽  
pp. 245-254 ◽  
Author(s):  
Åsa Blixt ◽  
Margit Mahlapuu ◽  
Marjo Aitola ◽  
Markku Pelto-Huikko ◽  
Sven Enerbäck ◽  
...  
Keyword(s):  
Lens Epithelium ◽  
Epithelial Proliferation ◽  
Proliferating Cells ◽  
Winged Helix ◽  
Lens Fibers ◽  
Lens Vesicle ◽  
Normal Lens ◽  
Winged Helix Transcription Factor ◽  
Forkhead Gene ◽  
Lens Placode

In the mouse mutant dysgenetic lens (dyl) the lens vesicle fails to separate from the ectoderm, causing a fusion between the lens and the cornea. Lack of a proliferating anterior lens epithelium leads to absence of secondary lens fibers and a dysplastic, cataractic lens. We report the cloning of a gene, FoxE3, encoding a forkhead/winged helix transcription factor, which is expressed in the developing lens from the start of lens placode induction and becomes restricted to the anterior proliferating cells when lens fiber differentiation begins. We show thatFoxE3 is colocalized with dyl in the mouse genome, thatdyl mice have mutations in the part of FoxE3 encoding the DNA-binding domain, and that these mutations cosegregate with thedyl phenotype. During embryonic development, the primordial lens epithelium is formed in an apparently normal way in dylmutants. However, instead of the proliferation characteristic of a normal lens epithelium, the posterior of these cells fail to divide and show signs of premature differentiation, whereas the most anterior cells are eliminated by apoptosis. This implies that FoxE3 is essential for closure of the lens vesicle and is a factor that promotes survival and proliferation, while preventing differentiation, in the lens epithelium.

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.

Different roles for Pax6 in the optic vesicle and facial epithelium mediate early morphogenesis of the murine eye

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 945-956 ◽  
Author(s):  
J.M. Collinson ◽  
R.E. Hill ◽  
J.D. West
Keyword(s):  
Histological Analysis ◽  
Eye Development ◽  
Wild Type Mouse ◽  
Lens Epithelium ◽  
Optic Vesicle ◽  
Wild Type ◽  
Adhesive Properties ◽  
Optic Vesicles ◽  
Lens Placode ◽  
Mutant Cells

Chimaeric mice were made by aggregating Pax6(−/−) and wild-type mouse embryos, in order to study the interaction between the optic vesicle and the prospective lens epithelium during early stages of eye development. Histological analysis of the distribution of homozygous mutant cells in the chimaeras showed that the cell-autonomous removal of Pax6(−/−) cells from the lens, shown previously at E12.5, is nearly complete by E9.5. Most mutant cells are eliminated from an area of facial epithelium wider than, but including, the developing lens placode. This result suggests a role for Pax6 in maintaining a region of the facial epithelium that has the tissue competence to undergo lens differentiation. Segregation of wild-type and Pax6(−/−) cells occurs in the optic vesicle at E9.5 and is most likely a result of different adhesive properties of wild-type and mutant cells. Also, proximo-distal specification of the optic vesicle (as assayed by the elimination of Pax6(−/−) cells distally), is disrupted in the presence of a high proportion of mutant cells. This suggests that Pax6 operates during the establishment of patterning along the proximo-distal axis of the vesicle. Examination of chimaeras with a high proportion of mutant cells showed that Pax6 is required in the optic vesicle for maintenance of contact with the overlying lens epithelium. This may explain why Pax6(−/−) optic vesicles are inefficient at inducing a lens placode. Contact is preferentially maintained when the lens epithelium is also wild-type. Together, these results demonstrate requirements for functional Pax6 in both the optic vesicle and surface epithelia in order to mediate the interactions between the two tissues during the earliest stages of eye development.

scholarly journals Graded phenotypic response to partial and complete deficiency of a brain-specific transcript variant of the winged helix transcription factor RFX4

Development ◽  
2003 ◽  
Vol 130 (19) ◽  
pp. 4539-4552 ◽  
Author(s):  
Perry J. Blackshear ◽  
Joan P. Graves ◽  
Deborah J. Stumpo ◽  
Inma Cobos ◽  
John L. R. Rubenstein ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcript Variant ◽  
Winged Helix ◽  
Specific Transcript ◽  
Phenotypic Response ◽  
Winged Helix Transcription Factor

The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1467-1479 ◽  
Author(s):  
R. Kos ◽  
M.V. Reedy ◽  
R.L. Johnson ◽  
C.A. Erickson
Keyword(s):  
Transcription Factors ◽  
Neural Crest ◽  
Antisense Oligonucleotides ◽  
Neural Crest Cells ◽  
Winged Helix ◽  
Dorsal Neural Tube ◽  
Neural Crest Development ◽  
Mesenchymal Transformation ◽  
Winged Helix Transcription Factor

The winged-helix or forkhead class of transcription factors has been shown to play important roles in cell specification and lineage segregation. We have cloned the chicken homolog of FoxD3, a member of the winged-helix class of transcription factors, and analyzed its expression. Based on its expression in the dorsal neural tube and in all neural crest lineages except the late-emigrating melanoblasts, we predicted that FoxD3 might be important in the segregation of the neural crest lineage from the neural epithelium, and for repressing melanogenesis in early-migrating neural crest cells. Misexpression of FoxD3 by electroporation in the lateral neural epithelium early in neural crest development produced an expansion of HNK1 immunoreactivity throughout the neural epithelium, although these cells did not undergo an epithelial/mesenchymal transformation. To test whether FoxD3 represses melanogenesis in early migrating neural crest cells, we knocked down expression in cultured neural crest with antisense oligonucleotides and in vivo by treatment with morpholino antisense oligonucleotides. Both experimental approaches resulted in an expansion of the melanoblast lineage, probably at the expense of neuronal and glial lineages. Conversely, persistent expression of FoxD3 in late-migrating neural crest cells using RCAS viruses resulted in the failure of melanoblasts to develop. We suggest that FoxD3 plays two important roles in neural crest development. First, it is involved in the segregation of the neural crest lineage from the neuroepithelium. Second, it represses melanogenesis, thereby allowing other neural crest derivatives to differentiate during the early stages of neural crest patterning.

scholarly journals The Winged Helix Transcription Factor Foxa3 Regulates Adipocyte Differentiation and Depot-Selective Fat Tissue Expansion

2013 ◽  
Vol 33 (17) ◽  
pp. 3392-3399 ◽  
Author(s):  
Lingyan Xu ◽  
Valentine Panel ◽  
Xinran Ma ◽  
Chen Du ◽  
Lynne Hugendubler ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Adipocyte Differentiation ◽  
Tissue Expansion ◽  
Fat Tissue ◽  
Winged Helix ◽  
Winged Helix Transcription Factor

scholarly journals Nucleosome positioning by the winged helix transcription factor HNF3

1998 ◽  
Vol 12 (1) ◽  
pp. 5-10 ◽  
Author(s):  
E. Y. Shim ◽  
C. Woodcock ◽  
K. S. Zaret
Keyword(s):  
Transcription Factor ◽  
Nucleosome Positioning ◽  
Winged Helix ◽  
Winged Helix Transcription Factor

scholarly journals Crystal Structure of the Virulence Gene Activator AphA fromVibrio choleraeReveals It Is a Novel Member of the Winged Helix Transcription Factor Superfamily

2005 ◽  
Vol 280 (14) ◽  
pp. 13779-13783 ◽  
Author(s):  
Rukman S. De Silva ◽  
Gabriela Kovacikova ◽  
Wei Lin ◽  
Ronald K. Taylor ◽  
Karen Skorupski ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Transcription Factor ◽  
Virulence Gene ◽  
Winged Helix ◽  
Winged Helix Transcription Factor
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