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.

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.

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.

scholarly journals Transvection at the eyes absent gene of Drosophila.

Genetics ◽  
1994 ◽  
Vol 138 (4) ◽  
pp. 1171-1179 ◽  
Author(s):  
W M Leiserson ◽  
N M Bonini ◽  
S Benzer
Keyword(s):  
Progenitor Cells ◽  
Gene Function ◽  
Compound Eye ◽  
Genome Rearrangements ◽  
Bithorax Complex ◽  
Eyes Absent ◽  
X Ray ◽  
Eye Size ◽  
General Rules

Abstract The Drosophila eyes absent (eya) gene is required for survival and differentiation of eye progenitor cells. Loss of gene function in the eye results in reduction or absence of the adult compound eye. Certain combinations of eya alleles undergo partial complementation, with dramatic restoration of eye size. This interaction is sensitive to the relative positions of the two alleles in the genome; rearrangements predicted to disrupt pairing of chromosomal homologs in the eya region disrupt complementation. Ten X-ray-induced rearrangements that suppress the interaction obey the same general rules as those that disrupt transvection at the bithorax complex and the decapentaplegic gene. Moreover, like transvection in those cases, the interaction at eya depends on the presence of normal zeste function. The discovery of transvection at eya suggests that transvection interactions of this type may be more prevalent than generally thought.

scholarly journals The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev185827
Author(s):  
Timothy Grocott ◽  
Estefania Lozano-Velasco ◽  
Gi Fay Mok ◽  
Andrea E. Münsterberg
Keyword(s):  
Model Organism ◽  
Control Gene ◽  
Tissue Interactions ◽  
Organ Systems ◽  
Necessary And Sufficient ◽  
Regenerative Therapies ◽  
Further Development ◽  
Master Control

ABSTRACTUnderstanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a ‘master control gene’ called Pax6, which is both necessary and sufficient for eye development. Yet precisely how Pax6 achieves this deeply homologous function is poorly understood. Using the chick as a model organism, we show that vertebrate Pax6 interacts with a pair of morphogen-coding genes, Tgfb2 and Fst, to form a putative Turing network, which we have computationally modelled. Computer simulations suggest that this gene network is sufficient to spontaneously polarise the developing retina, establishing the first organisational axis of the eye and prefiguring its further development. Our findings reveal how retinal self-organisation may be initiated independently of the highly ordered tissue interactions that help to assemble the eye in vivo. These results help to explain how stem cell aggregates spontaneously self-organise into functional eye-cups in vitro. We anticipate these findings will help to underpin retinal organoid technology, which holds much promise as a platform for disease modelling, drug development and regenerative therapies.

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 Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation

2012 ◽  
Vol 199 (3) ◽  
pp. 425-435 ◽  
Author(s):  
Bharat Joshi ◽  
Michele Bastiani ◽  
Scott S. Strugnell ◽  
Cecile Boscher ◽  
Robert G. Parton ◽  
...  
Keyword(s):  
Carcinoma Cells ◽  
Caveolin 1 ◽  
Early Growth Response ◽  
Breast Carcinoma Cells ◽  
Transcriptional Inhibition ◽  
Kinase C ◽  
Tyrosine 14 ◽  
Regulatory Loop ◽  
Early Growth Response 1 ◽  
The Relationship

Caveolin-1 (Cav1) is an essential component of caveolae whose Src kinase-dependent phosphorylation on tyrosine 14 (Y14) is associated with regulation of focal adhesion dynamics. However, the relationship between these disparate functions remains to be elucidated. Caveola biogenesis requires expression of both Cav1 and cavin-1, but Cav1Y14 phosphorylation is dispensable. In this paper, we show that Cav1 tyrosine phosphorylation induces caveola biogenesis via actin-dependent mechanotransduction and inactivation of the Egr1 (early growth response-1) transcription factor, relieving inhibition of endogenous Cav1 and cavin-1 genes. Cav1 phosphorylation reduces Egr1 binding to Cav1 and cavin-1 promoters and stimulates their activity. In MDA-231 breast carcinoma cells that express elevated levels of Cav1 and caveolae, Egr1 regulated Cav1, and cavin-1 promoter activity was dependent on actin, Cav1, Src, and Rho-associated kinase as well as downstream protein kinase C (PKC) signaling. pCav1 is therefore a mechanotransducer that acts via PKC to relieve Egr1 transcriptional inhibition of Cav1 and cavin-1, defining a novel feedback regulatory loop to regulate caveola biogenesis.

scholarly journals ThePax6master control gene initiates spontaneous retinal development via a self-organising Turing network

2019 ◽  
Author(s):  
Timothy Grocott ◽  
Estefania Lozano-Velasco ◽  
Gi Fay Mok ◽  
Andrea E Münsterberg
Keyword(s):  
Control Gene ◽  
Embryonic Tissues ◽  
Tissue Interactions ◽  
Organ Systems ◽  
Necessary And Sufficient ◽  
Regenerative Therapies ◽  
Further Development ◽  
Master Control

AbstractUnderstanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a ‘master control gene’ calledPax6, which is both necessary and sufficient for eye development1–6. Yet precisely howPax6achieves this deeply homologous function is poorly understood. Here we show that vertebratePax6interacts with a pair of morphogen-coding genes,Tgfb2andFst, to form a putative Turing network7, which we have computationally modelled. Computer simulations suggest that this gene network is sufficient to spontaneously polarise the developing retina, establishing the eye’s first organisational axis and prefiguring its further development. Our findings reveal how retinal self-organisation may be initiated independent of the highly ordered tissue interactions that help to assemble the eyein vivo. These results help to explain how stem cell aggregates spontaneously self-organise into functional eye-cupsin vitro8. We anticipate these findings will help to underpin retinal organoid technology, which holds much promise as a platform for disease modelling, drug development and regenerative therapies.

scholarly journals Introduction

Development ◽  
1987 ◽  
Vol 101 (Supplement) ◽  
pp. 1-1 ◽  
Author(s):  
Peter N. Goodfellow
Keyword(s):  
Sex Determination ◽  
Molecular Cloning ◽  
Genetic Control ◽  
Regulatory Genes ◽  
Control Gene ◽  
Developmental Control ◽  
Phenotypic Changes ◽  
Pleiotrophic Effects ◽  
Master Control ◽  
Testis Determining Gene

The current dogma describing the genetic control of development assumes a hierarchy of regulatory genes. In the simplest case, a master control gene directly regulates secondary genes which, in turn, regulate the expression of other genes. In principle the master control genes can be recognized by the pleiotrophic effects caused by mutation, however, complex phenotypic changes are also associated with mutations in many nonregulatory genes. The bestdescribed examples of control genes are from relatively simple organisms with well-developed genetics, for example Drosophila and Caenorhabdltis. Unfortunately, identification of developmental control genes in mammals has proved to be difficult, presumably because homeotic and similar mutations are lethal. There is, however, one well-defined developmental control gene in mammals: TDF or the testis-determining gene (the same locus is called Tdy in mouse). Molecular cloning of TDF will not only facilitate exploration of the fundamental questions of sex determination, but should also provide a model for genetic control of development.

Ommatidium assembly and formation of the retina—lamina projection in interspecific chimeras of cockroach

Development ◽  
1980 ◽  
Vol 60 (1) ◽  
pp. 345-358
Author(s):  
Mark S. Nowel
Keyword(s):  
Compound Eye ◽  
Cell Types ◽  
Axon Elongation ◽  
Leucophaea Maderae ◽  
Cone Cells ◽  
Suitable Target ◽  
Gromphadorhina Portentosa ◽  
Eye Formation

By grafting operations, interspecific eye chimeras of the cockroaches Gromphadorhina portentosa and Leucophaea maderae were produced. Mechanisms involved in the development of both the compound eye and the retina—lamina projection have been studied. Most cell types composing the eyes of these cockroaches are cytologically distinguishable in the chimera; also, retinula axons forming the retina-lamina projection in the two species are of vastly different lengths. At the border between host and graft eye tissue, individual ommatidia are formed containing cells of both types. In particular, it is shown that the four cone cells can be found in any of the possible combinations of the two cell types. This shows that the cone cells within one ommatidium are not necessarily related by lineage. These results are in agreement with the hypothesis that cells within an ommatidium are determined by position rather than by a lineage mechanism. Furthermore, formation of mosaic ommatidia suggests that mechanisms governing eye formation are similar in these two species. The formation of the projection from donor retina to host lamina shows that axon elongation is not rigidly programmed, but that the axons grow until they reach a suitable target at which point connexions are made.

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