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.

Mechanics of Optic Cup Invagination in the Embryonic Chick Eye

2012 ◽  
Author(s):  
Alina Oltean ◽  
David C. Beebe ◽  
Larry A. Taber
Keyword(s):  
Eye Development ◽  
Embryonic Chick ◽  
Optic Vesicle ◽  
Surface Ectoderm ◽  
Morphogenetic Process ◽  
Optic Cup ◽  
Optic Vesicles ◽  
Lens Vesicle ◽  
Lens Placode

Invagination of epithelia is an essential morphogenetic process that occurs in early eye development. The mechanics of the tissue forces necessary for eye invagination are not yet understood [1]. The eyes begin as two optic vesicles that grow outwards from the forebrain and adhere to the surface ectoderm. At this point of contact, both the surface ectoderm and optic vesicle thicken, forming the lens placode and retinal placode, respectively. The two placodes then bend inward to create the lens vesicle and bilayered optic cup (OC) [1, 2].

Interkinetic nuclear migration during the early stages of lens formation in the chicken embryo

Development ◽  
1969 ◽  
Vol 21 (1) ◽  
pp. 71-83
Author(s):  
Johan Zwaan ◽  
Phillips R. Bryan ◽  
Thomas L. Pearce
Keyword(s):  
Chicken Embryo ◽  
Morphological Changes ◽  
Fluorescent Antibody ◽  
Contact Period ◽  
Fluorescent Antibody Technique ◽  
Lens Protein ◽  
Surface Ectoderm ◽  
Antibody Technique ◽  
Lens Formation ◽  
Lens Placode

The optic vesicle in the chicken embryo, after growing out sufficiently to establish contact with the overlying ectoderm, adheres very firmly to the latter for a period of 12–15 h (McKeehan, 1951). Within the area of adhesion the surface ectoderm is transformed into a lens placode under influence of the developing retina. Little is known about the biochemical changes involved in this tissue transformation. Langman (1959) and Langman & Maisel (1962) found a cytotoxic effect of lens protein antisera and specific α-crystallin antibodies on presumptive lens cells shortly after induction had started but before the first morphological changes characteristic for the lens placode were visible. They concluded that the synthesis of α-crystallin might be a prerequisite for lens placode formation. Recent studies with the fluorescent antibody technique, however, indicate that the first crystallins are not produced until the very end of the contact period (Zwaan & Ikeda, 1965,1968; Ikeda & Zwaan, 1966).

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.

Pax6 is required for establishing naso-temporal and dorsal characteristics of the optic vesicle

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4535-4545 ◽  
Author(s):  
Nicole Bäumer ◽  
Till Marquardt ◽  
Anastassia Stoykova ◽  
Ruth Ashery-Padan ◽  
Kamal Chowdhury ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Eye Development ◽  
Genetic Network ◽  
Axis Formation ◽  
Pax6 Gene ◽  
Optic Vesicle ◽  
Intronic Enhancer ◽  
Key Factor ◽  
Lens Formation

The establishment of polarity is an important step during organ development. We assign a function for the paired and homeodomain transcription factor Pax6 in axis formation in the retina. Pax6 is a key factor of the highly conserved genetic network implicated in directing the initial phases of eye development. We recently demonstrated that Pax6 is also essential for later aspects of eye development, such as lens formation and retinogenesis. In this study, we present evidence that a highly conserved intronic enhancer, α, in the Pax6 gene is essential for the establishment of a distalhigh-proximallow gradient of Pax6 activity in the retina. In the mature retina, the activity mediated by the α-enhancer defines a population of retinal ganglion cells that project to two sickle-shaped domains in the superior colliculus and lateral geniculate nucleus. Deletion of the α-enhancer in vivo revealed that retinal Pax6 expression is regulated in two complementary topographic domains. We found that Pax6 activity is required for the establishment, as well as the maintenance of dorsal and nasotemporal characteristics in the optic vesicle and, later, the optic cup.

Delineation of transcriptional control signals within the Moloney murine sarcoma virus long terminal repeat

1985 ◽  
Vol 5 (8) ◽  
pp. 1948-1958
Author(s):  
B J Graves ◽  
R N Eisenman ◽  
S L McKnight
Keyword(s):  
Long Terminal Repeat ◽  
Transcriptional Control ◽  
Terminal Repeat ◽  
Control Element ◽  
Base Pairs ◽  
Mouse Fibroblasts ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Moloney Murine Sarcoma Virus ◽  
Murine Sarcoma

We identified three distinct elements within the Moloney murine sarcoma virus long terminal repeat that control transcription. The phenotypes of unidirectional deletion mutants of the long terminal repeat were assayed in microinjected frog oocytes and in transfected mouse fibroblasts. Steady-state levels of RNA bearing the same 5' terminus as the authentic Moloney murine sarcoma viral transcripts were measured by primer extension in assays that included a pseudo-wild-type internal reference. Mutant phenotypes define the boundaries of three functional elements. A region between 21 and 31 base pairs upstream from the mRNA cap site contains AT-rich sequences that function to establish the transcription start site. A second control element, termed the distal signal, lies between 31 and 84 base pairs upstream of the mRNA cap site. A CAT box consensus sequence is located at the 5' boundary of the distal signal. Additional components of the distal signal include a hexanucleotide sequence that is repeated four times. The distal signal augments transcription efficiency in oocytes but contributes only weakly to long terminal repeat-mediated expression in mouse fibroblasts. A third transcriptional control element lies between 156 and 364 base pairs upstream of the mRNA cap site. This element includes the 75-base-pair repeats previously identified as the Moloney murine sarcoma virus enhancer. In contrast to the distal signal, the Moloney murine sarcoma virus enhancer is crucial for significant expression in mouse fibroblasts but does not contribute to transcriptional expression in frog oocytes.

scholarly journals Simian virus 40 guanine-cytosine-rich sequences function as independent transcriptional control elements in vitro.

1984 ◽  
Vol 4 (12) ◽  
pp. 2911-2920 ◽  
Author(s):  
H Mishoe ◽  
J N Brady ◽  
M Radonovich ◽  
N P Salzman
Keyword(s):  
Rna Polymerase Ii ◽  
Dna Sequences ◽  
Base Pair ◽  
Transcriptional Control ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Control Element ◽  
Late Promoter ◽  
Transcription Control

We have recently shown that DNA sequences located within the simian virus 40 (SV40) G-C-rich, 21-base-pair repeats constitute an important transcriptional control element of the SV40 late promoter (Brady et al., Mol. Cell. Biol. 4:133-141, 1984). To gain further insight into the mechanism by which the SV40 G-C-rich repeats function, we have analyzed the transcriptional properties of several recombinant DNAs. The results presented in this report suggest that the SV40 G-C-rich sequences can function as independent RNA polymerase II transcriptional-control elements. In vitro competition studies demonstrated that sequences within the G-C-rich, 21-base-pair repeats, in the absence of either the SV40 early or late -25 transcriptional-control signals or the major RNA initiation sites, efficiently competed for transcription factors required for SV40 early and late RNA synthesis. Our transcription studies also demonstrated that in the absence of contiguous SV40 transcription control sequences, G-C-rich sequences stimulated initiation of transcription in a bidirectional manner, from proximally located sequences. Finally, we demonstrated that the 21-base-pair-repeat region can stimulate in vitro transcription from the heterologous adenovirus 2 major late promoter.

scholarly journals Characterization of a transcriptional control element involved in proliferation of peroxisomes in yeast in response to oleate

1993 ◽  
Vol 214 (1) ◽  
pp. 323-331 ◽  
Author(s):  
Alexandra W. C. EINERHAND ◽  
Wilko T. KOS ◽  
Ben DISTEL ◽  
Henk F. TABAK
Keyword(s):  
Transcriptional Control ◽  
Control Element

scholarly journals Sp1-Mediated Transcription of the Werner Helicase Gene Is Modulated by Rb and p53

1998 ◽  
Vol 18 (11) ◽  
pp. 6191-6200 ◽  
Author(s):  
Yukako Yamabe ◽  
Akira Shimamoto ◽  
Makoto Goto ◽  
Jun Yokota ◽  
Minoru Sugawara ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Promoter Activity ◽  
Transcriptional Control ◽  
Housekeeping Genes ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Luciferase Reporter ◽  
Upstream Region ◽  
Control Element ◽  
Mrna Levels

ABSTRACT The regulation of Werner’s syndrome gene (WRN) expression was studied by characterizing the cis-regulatory elements in the promoter region and the trans-activating factors that bind to them. First, we defined the transcription initiation sites and the sequence of the 5′ upstream region (2.8 kb) ofWRN that contains a number of cis-regulatory elements, including 7 Sp1, 9 retinoblastoma control element (RCE), and 14 AP2 motifs. A region consisting of nucleotides −67 to +160 was identified as the principal promoter of WRN by reporter gene assays in HeLa cells, using a series of WRNpromoter-luciferase reporter (WRN-Luc) plasmids that contained the 5′-truncated or mutated WRN upstream regions. In particular, two Sp1 elements proximal to the transcription initiation site are indispensable for WRN promoter activity and bind specifically to Sp1 proteins. The RCE enhances WRN promoter activity. Coexpression of the WRN-Luc plasmids with various dosages of plasmids expressing Rb or p53 in Saos2 cells lacking active Rb and p53 proteins showed that the introduced Rb upregulates WRN promoter activity a maximum of 2.5-fold, while p53 downregulates it a maximum of 7-fold, both dose dependently. Consistently, the overexpressed Rb and p53 proteins also affected the endogenous WRN mRNA levels in Saos2 cells, resulting in an increase with Rb and a decrease with p53. These findings suggest that WRN expression, like that of other housekeeping genes, is directed mainly by the Sp1 transcriptional control system but is also further modulated by transcription factors, including Rb and p53, that are implicated in the cell cycle, cell senescence, and genomic instability.

scholarly journals Rubella cataract in vitro: Sensitive period of the developing human lens.

1975 ◽  
Vol 141 (6) ◽  
pp. 1238-1248 ◽  
Author(s):  
M Karkinen-Jääskeläinen ◽  
L Saxén ◽  
A Vaheri ◽  
P Leinikki
Keyword(s):  
Clinical Findings ◽  
Lens Capsule ◽  
Human Lens ◽  
Sensitive Period ◽  
Fiber Damage ◽  
Viral Antigens ◽  
Lens Vesicle ◽  
Lens Placode ◽  
Made In

The clinically known sensitive period of rubella cataract was studied in vitro by infecting 79 human eye rudiments from embryos aged 4-10 wk with rubella virus. The course of the infection was followed by histological and indirect immunofluorescence methods. Of the rudiments, 12 pairs were in the lens placode or open-lens-vesicle stage, 40 already had closed lens vesicles and in another 27 closed-stage pairs an incision was made in the lens capsule before infection to allow the virus to enter the lens. Uninfected controls differentiated well in vitro for 4-6 wk. The eye rudiments infected in the open-lens-vesicle stage showed lens fiber destruction and viral antigens within the lens. No damage or viral antigens were detected in rudiments infected in the closed stage unless the lens capsule was incisedmwhen this was done, however, fiber damage ensued and viral antigens appeared. The lens capsule was concluded to form a protective barrier around the sensirive fibers at the time of closure of the lens vesicle, confirming the earlier hypothesis and clinical findings.

scholarly journals Transcription factor IIIA gene expression in Xenopus oocytes utilizes a transcription factor similar to the major late transcription factor.

1989 ◽  
Vol 9 (11) ◽  
pp. 5003-5011 ◽  
Author(s):  
R K Hall ◽  
W L Taylor
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Control ◽  
Somatic Cells ◽  
State Level ◽  
Control Element ◽  
Transcription Factor Iiia ◽  
Shift Analysis ◽  
Late Transcription ◽  
Upstream Element

Xenopus transcription factor IIIA (TFIIIA) gene expression is stringently regulated during development. The steady-state level of TFIIIA mRNA in a somatic cell is approximately 10(6) times less than in an immature oocyte. We have undertaken studies designed to identify differences in how the TFIIIA gene is transcribed in oocytes and somatic cells. In this regard, we have localized an upstream transcriptional control element in the TFIIIA promoter that stimulates transcription from the TFIIIA promoter approximately threefold in microinjected oocytes. The upstream element, in cis. does not stimulate transcription from the TFIIIA promoter in somatic cells. Thus, the element appears to be oocyte specific in the context of the TFIIIA promoter. However, both oocytes and somatic cells contain a protein (or a related protein) that binds the upstream element. We have termed this protein from oocytes the TFIIIA distal element factor. The sequence of the upstream element is similar to the sequence of the upstream element found in the adenovirus major late promoter that is a binding site for the major late transcription factor. By gel shift analysis, chemical footprinting, methylation intereference, and point mutation analysis, we demonstrate that the TFIIIA distal element factor and major late transcription factor have similar DNA-binding properties.

Sign in / Sign up

Export Citation Format

Share Document