Antagonistic regulation of the second mitotic wave by Eyes absent-Sine oculis and Combgap coordinates proliferation and specification in theDrosophilaretina

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.

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Dpp and Hh signaling in the Drosophila embryonic eye field

Development ◽

10.1242/dev.128.23.4691 ◽

2001 ◽

Vol 128 (23) ◽

pp. 4691-4704 ◽

Cited By ~ 2

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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Signaling by the TGF-beta homolog decapentaplegic functions reiteratively within the network of genes controlling retinal cell fate determination in Drosophila

Development ◽

10.1242/dev.126.5.935 ◽

1999 ◽

Vol 126 (5) ◽

pp. 935-943 ◽

Cited By ~ 12

Author(s):

R. Chen ◽

G. Halder ◽

Z. Zhang ◽

G. Mardon

Keyword(s):

Cell Fate ◽

Retinal Cell ◽

Cell Fate Determination ◽

Tgf Beta ◽

Eyes Absent ◽

Fate Determination ◽

Sine Oculis ◽

Retinal Determination ◽

Interactive Network ◽

Distinct Cell

Retinal cell fate determination in Drosophila is controlled by an interactive network of genes, including eyeless, eyes absent, sine oculis and dachshund. We have investigated the role of the TGF-beta homolog decapentaplegic in this pathway. We demonstrate that, during eye development, while eyeless transcription does not depend on decapentaplegic activity, the expression of eyes absent, sine oculis and dachshund are greatly reduced in a decapentaplegic mutant background. We also show that decapentaplegic signaling acts synergistically with and at multiple levels of the retinal determination network to induce eyes absent, sine oculis and dachshund expression and ectopic eye formation. These results suggest a mechanism by which a general patterning signal such as Decapentaplegic cooperates reiteratively with tissue-specific factors to determine distinct cell fates during development.

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Functional analysis of the role of eyes absent and sine oculis in the developing eye of the cricket Gryllus bimaculatus

Development Growth & Differentiation ◽

10.1111/j.1440-169x.2011.01325.x ◽

2012 ◽

Vol 54 (2) ◽

pp. 227-240 ◽

Cited By ~ 16

Author(s):

Akira Takagi ◽

Kazuki Kurita ◽

Taiki Terasawa ◽

Taro Nakamura ◽

Tetsuya Bando ◽

...

Keyword(s):

Functional Analysis ◽

Gryllus Bimaculatus ◽

Eyes Absent ◽

Sine Oculis

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

Development ◽

10.1242/dev.125.12.2181 ◽

1998 ◽

Vol 125 (12) ◽

pp. 2181-2191 ◽

Cited By ~ 15

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.

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Molecular Analysis of Drosophilaeyes absentMutants Reveals Features of the Conserved Eya Domain

Genetics ◽

10.1093/genetics/155.2.709 ◽

2000 ◽

Vol 155 (2) ◽

pp. 709-720 ◽

Cited By ~ 2

Author(s):

Quang T Bui ◽

John E Zimmerman ◽

Haixi Liu ◽

Nancy M Bonini

Keyword(s):

Protein Sequence ◽

Molecular Genetic ◽

Molecular Genetic Analysis ◽

Special Importance ◽

Missense Mutations ◽

Eyes Absent ◽

Sine Oculis ◽

Eye Formation

AbstractThe eyes absent (eya) gene is critical to eye formation in Drosophila; upon loss of eya function, eye progenitor cells die by programmed cell death. Moreover, ectopic eya expression directs eye formation, and eya functionally synergizes in vivo and physically interacts in vitro with two other genes of eye development, sine oculis and dachshund. The Eya protein sequence, while highly conserved to vertebrates, is novel. To define amino acids critical to the function of the Eya protein, we have sequenced eya alleles. These mutations have revealed that loss of the entire Eya Domain is null for eya activity, but that alleles with truncations within the Eya Domain display partial function. We then extended the molecular genetic analysis to interactions within the Eya Domain. This analysis has revealed regions of special importance to interaction with Sine Oculis or Dachshund. Select eya missense mutations within the Eya Domain diminished the interactions with Sine Oculis or Dachshund. Taken together, these data suggest that the conserved Eya Domain is critical for eya activity and may have functional subregions within it.

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Genetic dissection of the Transcription Factor code controlling serial specification of muscle identities in Drosophila

eLife ◽

10.7554/elife.14979 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 10

Author(s):

Laurence Dubois ◽

Jean-Louis Frendo ◽

Hélène Chanut-Delalande ◽

Michèle Crozatier ◽

Alain Vincent

Keyword(s):

Transcriptional Control ◽

Developmental Time ◽

Genetic Dissection ◽

Eyes Absent ◽

Transcription Start Sites ◽

Sine Oculis ◽

Evolutionary Diversification ◽

Dynamic View ◽

Alternative Transcription ◽

Myogenic Factors

Each Drosophila muscle is seeded by one Founder Cell issued from terminal division of a Progenitor Cell (PC). Muscle identity reflects the expression by each PC of a specific combination of identity Transcription Factors (iTFs). Sequential emergence of several PCs at the same position raised the question of how developmental time controlled muscle identity. Here, we identified roles of Anterior Open and ETS domain lacking in controlling PC birth time and Eyes absent, No Ocelli, and Sine oculis in specifying PC identity. The windows of transcription of these and other TFs in wild type and mutant embryos, revealed a cascade of regulation integrating time and space, feed-forward loops and use of alternative transcription start sites. These data provide a dynamic view of the transcriptional control of muscle identity in Drosophila and an extended framework for studying interactions between general myogenic factors and iTFs in evolutionary diversification of muscle shapes.

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Direct regulatory interaction of the eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila

Development ◽

10.1242/dev.126.10.2253 ◽

1999 ◽

Vol 126 (10) ◽

pp. 2253-2260 ◽

Cited By ~ 10

Author(s):

T. Niimi ◽

M. Seimiya ◽

U. Kloter ◽

S. Flister ◽

W.J. Gehring

Keyword(s):

Target Genes ◽

Ectopic Expression ◽

Direct Interaction ◽

Loss Of Function ◽

Eyes Absent ◽

Sine Oculis ◽

Dna Binding Domains ◽

Binding Domains ◽

Eye Morphogenesis

The Pax-6 gene encodes a transcription factor with two DNA-binding domains, a paired and a homeodomain, and is expressed during eye morphogenesis and development of the nervous system. Pax-6 homologs have been isolated from a wide variety of organisms ranging from flatworms to humans. Since loss-of-function mutants in insects and mammals lead to an eyeless phenotype and Pax-6 orthologs from distantly related species are capable of inducing ectopic eyes in Drosophila, we have proposed that Pax-6 is a universal master control gene for eye morphogenesis. To determine the extent of evolutionary conservation of the eye morphogenetic pathway, we have begun to identify subordinate target genes of Pax-6. Previously we have shown that expression of two genes, sine oculis (so) and eyes absent (eya), is induced by eyeless (ey), the Pax-6 homolog of Drosophila. Here we present evidence from ectopic expression studies in transgenic flies, from transcription activation studies in yeast, and from gel shift assays in vitro that the EY protein activates transcription of sine oculis by direct interaction with an eye-specific enhancer in the long intron of the so gene.

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Differential interactions ofeyelessandtwin of eyelesswith thesine oculisenhancer

Development ◽

10.1242/dev.129.3.625 ◽

2002 ◽

Vol 129 (3) ◽

pp. 625-634 ◽

Cited By ~ 4

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.

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