Differential interactions ofeyelessandtwin of eyelesswith thesine oculisenhancer

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 625-634 ◽  
Author(s):  
Claudio Punzo ◽  
Makiko Seimiya ◽  
Susanne Flister ◽  
Walter J. Gehring ◽  
Serge Plaza
Keyword(s):  
Binding Sites ◽  
Compound Eye ◽  
Eye Development ◽  
Targeted Mutagenesis ◽  
Hierarchical Network ◽  
Eyes Absent ◽  
Sine Oculis ◽  
Visual Systems ◽  
Rescue Experiment ◽  
Functional Involvement

Drosophila eye development is under the control of early eye specifying genes including eyeless (ey), twin of eyeless (toy), eyes absent (eya), dachshund (dac) and sine oculis (so). They are all conserved between vertebrates and insects and they interact in a combinatorial and hierarchical network to regulate each other expression. so has been shown to be directly regulated by ey through an eye-specific enhancer (so10). We further studied the regulation of this element and found that both Drosophila Pax6 proteins namely EY and TOY bind and positively regulate so10 expression through different binding sites. By targeted mutagenesis experiments, we disrupted these EY and TOY binding sites and studied their functional involvement in the so10 enhancer expression in the eye progenitor cells. We show a differential requirement for the EY and TOY binding sites in activating so10 during the different stages of eye development. Additionally, in a rescue experiment performed in the so1 mutant, we show that the EY and TOY binding sites are required for compound eye and ocellus development respectively. Altogether, these results suggest a differential requirement for EY and TOY to specify the development of the two types of adult visual systems, namely the compound eye and the ocellus.

Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2181-2191 ◽  
Author(s):  
G. Halder ◽  
P. Callaerts ◽  
S. Flister ◽  
U. Walldorf ◽  
U. Kloter ◽  
...  
Keyword(s):  
Feedback Loop ◽  
Compound Eye ◽  
Eye Development ◽  
Positive Feedback Loop ◽  
Eyes Absent ◽  
Regulatory Interactions ◽  
Sine Oculis ◽  
Eye Disc ◽  
Embryonic Head ◽  
Genetic Hierarchy

The Drosophila Pax-6 gene eyeless acts high up in the genetic hierarchy involved in compound eye development and can direct the formation of extra eyes in ectopic locations. Here we identify sine oculis and eyes absent as two mediators of the eye-inducing activity of eyeless. We show that eyeless induces and requires the expression of both genes independently during extra eye development. During normal eye development, eyeless is expressed earlier than and is required for the expression of sine oculis and eyes absent, but not vice versa. Based on the results presented here and those of others, we propose a model in which eyeless induces the initial expression of both sine oculis and eyes absent in the eye disc. sine oculis and eyes absent then appear to participate in a positive feedback loop that regulates the expression of all three genes. In contrast to the regulatory interactions that occur in the developing eye disc, we also show that in the embryonic head, sine oculis acts in parallel to eyeless and twin of eyeless, a second Pax-6 gene from Drosophila. Recent studies in vertebrate systems indicate that the epistatic relationships among the corresponding vertebrate homologs are very similar to those observed in Drosophila.

The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4819-4826 ◽  
Author(s):  
N.M. Bonini ◽  
Q.T. Bui ◽  
G.L. Gray-Board ◽  
J.M. Warrick
Keyword(s):  
Gene Function ◽  
Compound Eye ◽  
Eye Development ◽  
Control Gene ◽  
Eyes Absent ◽  
Regulatory Loop ◽  
The Relationship ◽  
Eye Formation ◽  
Master Control

The fly eyes absent (eya) gene which is essential for compound eye development in Drosophila, was shown to be functionally replaceable in eye development by a vertebrate Eya homolog. The relationship between eya and that of the eyeless gene, a Pax-6 homolog, critical for eye formation in both flies and man, was defined: eya was found to be essential for eye formation by eyeless. Moreover, eya could itself direct ectopic eye formation, indicating that eya has the capacity to function as a master control gene for eye formation. Finally, we show that eya and eyeless together were more effective in eye formation than either gene alone. These data indicate conservation of the pathway of eya function between flies and vertebrates; they suggest a model whereby eya/Eya gene function is essential for eye formation by eyeless/Pax-6, and that eya/Eya can in turn mediate, via a regulatory loop, the activity of eyeless/Pax-6 in eye formation.

scholarly journals Morphogenetic furrow initiation and progression during eye development in Drosophila: the roles of decapentaplegic, hedgehog and eyes absent

Development ◽  
2000 ◽  
Vol 127 (6) ◽  
pp. 1325-1336 ◽  
Author(s):  
J. Curtiss ◽  
M. Mlodzik
Keyword(s):  
Eye Development ◽  
Loss Of Function ◽  
Morphogenetic Furrow ◽  
Eyes Absent ◽  
Sine Oculis ◽  
Functional Relationships ◽  
Eye Disc ◽  
Additional Control ◽  
Redundant Functions ◽  
Signaling Components

The Drosophila signaling factor decapentaplegic (dpp) mediates the effects of hedgehog (hh) in tissue patterning by regulating the expression of tissue-specific genes. In the eye disc, the transcription factors eyeless (ey), eyes absent (eya), sine oculis (so) and dachshund (dac) participate with these signaling molecules in a complex regulatory network that results in the initiation of eye development. Our analysis of functional relationships in the early eye disc indicates that hh and dpp play no role in regulating ey, but are required for eya, so and dac expression. We show that restoring expression of eya in loss-of-function dpp mutant backgrounds is sufficient to induce so and dac expression and to rescue eye development. Thus, once expressed, eya can carry out its functions in the absence of dpp. These experiments indicate that dpp functions downstream of or in parallel with ey, but upstream of eya, so and dac. Additional control is provided by a feedback loop that maintains expression of eya and so and includes dpp. The fact that exogenous overexpression of ey, eya, so and dac interferes with wild-type eye development demonstrates the importance of such a complicated mechanism for maintaining proper levels of these factors during early eye development. Whereas initiation of eye development fails in either Hh or Dpp signaling mutants, the subsequent progression of the morphogenetic furrow is only slowed down. However, we find that clones that are simultaneously mutant for Hh and Dpp signaling components completely block furrow progression and eye differentiation, suggesting that Hh and Dpp serve partially redundant functions in this process. Interestingly, furrow-associated expression of eya, so and dac is not affected by double mutant tissue, suggesting that some other factor(s) regulates their expression during furrow progression.

Functional Involvement of Thrombospondin in Platelet Aggregation Induced by Low Versus High Concentrations of Thrombin

1986 ◽  
Vol 55 (01) ◽  
pp. 136-142 ◽  
Author(s):  
K J Kao ◽  
David M Shaut ◽  
Paul A Klein
Keyword(s):  
Platelet Aggregation ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Activated Platelets ◽  
Low Concentrations ◽  
Platelet Binding ◽  
Functional Involvement ◽  
Thrombin Activation ◽  
Platelet Aggregates ◽  
High Concentrations

SummaryThrombospondin (TSP) is a major platelet secretory glycoprotein. Earlier studies of various investigators demonstrated that TSP is the endogenous platelet lectin and is responsible for the hemagglutinating activity expressed on formaldehyde-fixed thrombin-treated platelets. The direct effect of highly purified TSP on thrombin-induced platelet aggregation was studied. It was observed that aggregation of gel-filtered platelets induced by low concentrations of thrombin (≤0.05 U/ml) was progressively inhibited by increasing concentrations of exogenous TSP (≥60 μg/ml). However, inhibition of platelet aggregation by TSP was not observed when higher than 0.1 U/ml thrombin was used to activate platelets. To exclude the possibility that TSP inhibits platelet aggregation by affecting thrombin activation of platelets, three different approaches were utilized. First, by using a chromogenic substrate assay it was shown that TSP does not inhibit the proteolytic activity of thrombin. Second, thromboxane B2 synthesis by thrombin-stimulated platelets was not affected by exogenous TSP. Finally, electron microscopy of thrombin-induced platelet aggregates showed that platelets were activated by thrombin regardless of the presence or absence of exogenous TSP. The results indicate that high concentrations of exogenous TSP (≥60 μg/ml) directly interfere with interplatelet recognition among thrombin-activated platelets. This inhibitory effect of TSP can be neutralized by anti-TSP Fab. In addition, anti-TSP Fab directly inhibits platelet aggregation induced by a low (0.02 U/ml) but not by a high (0.1 U/ml) concentration of thrombin. In conclusion, our findings demonstrate that TSP is functionally important for platelet aggregation induced by low (≤0.05 U/ml) but not high (≥0.1 U/ml) concentrations of thrombin. High concentrations of exogenous TSP may univalently saturate all its platelet binding sites consequently interfering with TSP-crosslinking of thrombin-activated platelets.

The Drosophila homeobox gene optix is capable of inducing ectopic eyes by an eyeless-independent mechanism

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1879-1886 ◽  
Author(s):  
M. Seimiya ◽  
W.J. Gehring
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Gene Family ◽  
Eye Development ◽  
Ectopic Expression ◽  
Amino Acid Sequence Similarity ◽  
Sine Oculis ◽  
High Amino Acid ◽  
Independent Mechanism ◽  
Ectopic Eyes

optix is a new member of the Six/so gene family from Drosophila that contains both a six domain and a homeodomain. Because of its high amino acid sequence similarity with the mouse Six3 gene, optix is considered to be the orthologous gene from Drosophila rather than sine oculis, as previously believed. optix expression was detected in the eye, wing and haltere imaginal discs. Ectopic expression of optix leads to the formation of ectopic eyes suggesting that optix has important functions in eye development. Although optix and sine oculis belong to the same gene family (Six/so) and share a high degree of amino acid sequence identity, there are a number of factors which suggest that their developmental roles are different: (1) the expression patterns of optix and sine oculis are clearly distinct; (2) sine oculis acts downstream of eyeless, whereas optix is expressed independently of eyeless; (3) sine oculis functions synergistically with eyes absent in eye development whereas optix does not; (4) ectopic expression of optix alone, but not of sine oculis can induce ectopic eyes in the antennal disc. These results suggest that optix is involved in eye morphogenesis by an eyeless-independent mechanism.

Three-Dimensional Time-Lapse Digital Movie Analysis of the Developing Fruit Fly Eye in Organ Culture

1997 ◽  
Vol 3 (S2) ◽  
pp. 1129-1130
Author(s):  
John Archie Pollock ◽  
Bejon T. Maneckshana ◽  
Teresa E. Leonardo
Keyword(s):  
Organ Culture ◽  
Compound Eye ◽  
Eye Development ◽  
Larval Instar ◽  
Three Dimensional ◽  
Fruit Fly ◽  
Time Lapse ◽  
Cell Types ◽  
Specific Cell ◽  
The Brain

The compound eye of the fruit fly, Drosophila melanogaster, is composed of a highly ordered array of facets (FIG. 1), each containing a precise set of neurons and supporting cells. The eye arises during the third larval instar from an undifferentiated epithelium, the eye imaginai disc, which is connected to the brain via the optic stalk (FIG. 2). During eye development, movement of the morphogenetic furrow, progressive recruitment of specific cell types and the growth of photoreceptor axons into the brain are each dynamic processes that are routinely studied indirectly in fixed tissues. While stereotyped development and the ‘crystalline’ like structure of the eye facilitates this analysis, certain experiments are hindered by the inability to observe developmental processes as they occur. To overcome this limitation, we have combined organ culture with advanced microscopy tools to enable the observation of eye development in living tissue.

scholarly journals Identification of novel direct targets of Drosophila Sine oculis and Eyes absent by integration of genome-wide data sets

2016 ◽  
Vol 415 (1) ◽  
pp. 157-167 ◽  
Author(s):  
Meng Jin ◽  
Sara Aibar ◽  
Zhongqi Ge ◽  
Rui Chen ◽  
Stein Aerts ◽  
...  
Keyword(s):  
Data Sets ◽  
Eyes Absent ◽  
Sine Oculis ◽  
Genome Wide ◽  
Genome Wide Data

scholarly journals Transcriptional regulation of atonal required for Drosophila larval eye development by concerted action of eyes absent, sine oculis and hedgehog signaling independent of fused kinase and cubitus interruptus

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1531-1540 ◽  
Author(s):  
T. Suzuki ◽  
K. Saigo
Keyword(s):  
Hedgehog Signaling ◽  
Specific Antigen ◽  
Photoreceptor Cells ◽  
Organ Development ◽  
Cubitus Interruptus ◽  
Eyes Absent ◽  
Organ Formation ◽  
Sine Oculis ◽  
Founder Cells ◽  
Bolwig's Organ

Bolwig's organ is the larval light-sensing system consisting of 12 photoreceptors and its development requires atonal activity. Here, we showed that Bolwig's organ formation and atonal expression are controlled by the concerted function of hedgehog, eyes absent and sine oculis. Bolwig's organ primordium was first detected as a cluster of about 14 Atonal-positive cells at the posterior edge of the ocular segment in embryos and hence, atonal expression may define the region from which a few Atonal-positive founder cells (future primary photoreceptor cells) are generated by lateral specification. In Bolwig's organ development, neural differentiation precedes photoreceptor specification, since Elav, a neuron-specific antigen, whose expression is under the control of atonal, is expressed in virtually all early-Atonal-positive cells prior to the establishment of founder cells. Neither Atonal expression nor Bolwig's organ formation occurred in the absence of hedgehog, eyes absent or sine oculis activity. Genetic and histochemical analyses indicated that (1) responsible Hedgehog signals derive from the ocular segment, (2) Eyes absent and Sine oculis act downstream of or in parallel with Hedgehog signaling and (3) the Hedgehog signaling pathway required for Bolwig's organ development is a new type and lacks Fused kinase and Cubitus interruptus as downstream components.

Dpp and Hh signaling in the Drosophila embryonic eye field

Development ◽  
2001 ◽  
Vol 128 (23) ◽  
pp. 4691-4704 ◽  
Author(s):  
Ting Chang ◽  
Julie Mazotta ◽  
Karin Dumstrei ◽  
Andra Dumitrescu ◽  
Volker Hartenstein
Keyword(s):  
Optic Lobe ◽  
Drosophila Embryo ◽  
Signal Loss ◽  
Fate Map ◽  
Dorsal Midline ◽  
Eyes Absent ◽  
Sine Oculis ◽  
Eye Field ◽  
Hh Signaling ◽  
Hypomorphic Alleles

We have analyzed the function of the Decapentaplegic (Dpp) and Hedgehog (Hh) signaling pathways in partitioning the dorsal head neurectoderm of the Drosophila embryo. This region, referred to as the anterior brain/eye anlage, gives rise to both the visual system and the protocerebrum. The anlage splits up into three main domains: the head midline ectoderm, protocerebral neurectoderm and visual primordium. Similar to their vertebrate counterparts, Hh and Dpp play an important role in the partitioning of the anterior brain/eye anlage. Dpp is secreted in the dorsal midline of the head. Lowering Dpp levels (in dpp heterozygotes or hypomorphic alleles) results in a ‘cyclops’ phenotype, where mid-dorsal head epidermis is transformed into dorsolateral structures, i.e. eye/optic lobe tissue, which causes a continuous visual primordium across the dorsal midline. Absence of Dpp results in the transformation of both dorsomedial and dorsolateral structures into brain neuroblasts. Regulatory genes that are required for eye/optic lobe fate, including sine oculis (so) and eyes absent (eya), are turned on in their respective domains by Dpp. The gene zerknuellt (zen), which is expressed in response to peak levels of Dpp in the dorsal midline, secondarily represses so and eya in the dorsomedial domain. Hh and its receptor/inhibitor, Patched (Ptc), are expressed in a transverse stripe along the posterior boundary of the eye field. As reported previously, Hh triggers the expression of determinants for larval eye (atonal) and adult eye (eyeless) in those cells of the eye field that are close to the Hh source. Eya and So, which are induced by Dpp, are epistatic to the Hh signal. Loss of Ptc, as well as overexpression of Hh, results in the ectopic induction of larval eye tissue in the dorsal midline (cyclopia). We discuss the similarities between vertebrate systems and Drosophila with regard to the fate map of the anterior brain/eye anlage, and its partitioning by Dpp and Hh signaling.

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