Dual regulation and redundant function of two eye-specific enhancers of the<i>Drosophila</i>retinal determination gene<i>dachshund</i>

Pappu, Kartik S.; Ostrin, Edwin J.; Middlebrooks, Brooke W.; Sili, Beril Tavsanli; Chen, Rui; Atkins, Mardelle; Gibbs, Richard A.; Mardon, Graeme

doi:10.1242/dev.01869

Cited by 73 publications

(100 citation statements)

References 55 publications

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“…Because Dac already is expressed in the IPC lineage at the embryonic stage (10, 11), we examined whether dac is required for the initial specification and neuronal differentiation of IPCs. dac 3 genetic-null homozygous mutants are lethal during the pupal stage, and these mutants exhibit severe defects in eye development (22,23). However, the cell number, neuronal morphology, and projection patterns in the dac-mutant larvae were indistinguishable from those in the control (Fig.…”

Section: Resultsmentioning

confidence: 96%

Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression

Okamoto¹,

Nishimori²,

Nishimura³

2012

Proc. Natl. Acad. Sci. U.S.A.

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Members of the insulin family peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. The Drosophila genome encodes seven insulin-like peptide genes, dilp1-7, and the most prominent dilps (dilp2, dilp3, and dilp5) are expressed in brain neurosecretory cells known as "insulin-producing cells" (IPCs). Although these dilps are expressed in the same cells, the expression of each dilp is regulated independently. However, the molecular mechanisms that regulate the expression of individual dilps in the IPCs remain largely unknown. Here, we show that Dachshund (Dac), which is a highly conserved nuclear protein, is a critical transcription factor that specifically regulates dilp5 expression. Dac was strongly expressed in IPCs throughout development. dac loss-of-function analyses revealed a severely reduced dilp5 expression level in young larvae. Dac interacted physically with the Drosophila Pax6 homolog Eyeless (Ey), and these proteins synergistically promoted dilp5 expression. In addition, the mammalian homolog of Dac, Dach1/2, facilitated the promoting action of Pax6 on the expression of islet hormone genes in cultured mammalian cells. These observations indicate the conserved role of Dac/Dach in controlling insulin expression in conjunction with Ey/Pax6.

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Section: Resultsmentioning

confidence: 96%

Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression

Okamoto¹,

Nishimori²,

Nishimura³

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…24) was used to build a lamina-specific FLP transgene. A NotI-BamHI fragment containing the entire FLP coding region and a simian virus 40 (SV40)-poly(A) tail from the UAS-FLP vector (gift from J. Duffy) was cloned into the NotI-BamHI-digested pCasper-4.…”

Section: Construction Of a Lamina Neuron-specific Flp Sourcementioning

confidence: 99%

Dscam2 mediates axonal tiling in the Drosophila visual system

Millard

Flanagan²,

Pappu³

et al. 2007

Nature

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144

211

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Sensory processing centres in both the vertebrate and the invertebrate brain are often organized into reiterated columns, thus facilitating an internal topographic representation of the external world. Cells within each column are arranged in a stereotyped fashion and form precise patterns of synaptic connections within discrete layers. These connections are largely confined to a single column, thereby preserving the spatial information from the periphery. Other neurons integrate this information by connecting to multiple columns. Restricting axons to columns is conceptually similar to tiling. Axons and dendrites of neighbouring neurons of the same class use tiling to form complete, yet non-overlapping, receptive fields1-3. It is thought that, at the molecular level, cellsurface proteins mediate tiling through contact-dependent repulsive interactions1,2,4,5, but proteins serving this function have not yet been identified. Here we show that the immunoglobulin superfamily member Dscam2 restricts the connections formed by L1 lamina neurons to columns in the Drosophila visual system. Our data support a model in which Dscam2 homophilic interactions mediate repulsion between neurites of L1 cells in neighbouring columns. We propose that Dscam2 is a tiling receptor for L1 neurons.The Drosophila visual system is a modular structure6,7. The retina contains 750 simple eyes, each containing eight photoreceptor neurons or R cells (R1-R8). R cells project into the brain, where they make connections within two neuropils, the lamina and medulla. R1-R6 neurons target to the lamina, where they form synapses with lamina neurons (L1-L5). R7, R8 and L1-L5 form connections in single columns within layers in the medulla, and each column contains one axon of each of these cell types. As a consequence of this wiring pattern, each column processes motion (lamina neurons) and colour (R7 and R8) from a single point in space6. Although some progress has been made in understanding how neurons select different layers within each of the 750 columns6, the molecular mechanisms that restrict synaptic connections to a single column are not known.Dscam2 belongs to a conserved family of cell-surface proteins expressed in the nervous systems of many different organisms8-10. Down syndrome cell adhesion molecule (DSCAM) was originally identified as an open reading frame in a region of human chromosome 21 critical for Down's syndrome11. There are four Dscam genes in the fly genome (Dscam,. They encode type I transmembrane proteins that share about 30% sequence identity and have a common extracellular domain comprising ten ©2007 Nature Publishing GroupCorrespondence and requests for materials should be addressed to S.L.Z. (lzipursky@mednet.ucla.edu).. Full Methods and any associated references are available in the online version of the paper at www.nature.com/nature.Supplementary Information is linked to the online version of the paper at www.nature.com/nature.Reprints and permissions information is available at www.nature.com/reprints. The Dscam...

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“…Over the last few years, Ey and So have been shown to play a crucial role in the deployment and maintenance of the RD network by directly regulating the transcription of several eye-specification genes [ey, so, eya, dachshund (dac) and optix] (Niimi et al, 1999;Punzo et al, 2002;Ostrin et al, 2006;Pappu et al, 2005;Pauli et al, 2005). However, little is known about downstream targets of the RD cascade.…”

Section: Direct Control Of Ato By a Potential Ey-so Complexmentioning

confidence: 99%

Direct control of neurogenesis by selector factors in the fly eye:regulation ofatonalby Ey and So

et al. 2006

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During eye development, the selector factors of the Eyeless/Pax6 or Retinal Determination (RD) network control specification of organ-type whereas the bHLH-type proneural factor Atonal drives neurogenesis. Although significant progress has been made in dissecting the acquisition of 'eye identity' at the transcriptional level, the molecular mechanisms underlying the progression from neuronal progenitor to differentiating neuron remain unclear. A recently proposed model for the integration of organ specification and neurogenesis hypothesizes that atonal expression in the eye is RD-network-independent and that Eyeless works in parallel or downstream of atonal to modify the neurogenetic program. We show here that distinct cis-regulatory elements control atonal expression specifically in the eye and that the RD factors Eyeless and Sine oculis function as direct regulators. We find that these transcription factors interact in vitro and provide indirect evidence that this interaction may be required in vivo. The subordination of neurogenesis to the RD pathway in the eye provides a direct mechanism for the coordination of neurogenesis and tissue specification during sensory organ formation.

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Dual regulation and redundant function of two eye-specific enhancers of theDrosophilaretinal determination genedachshund

Cited by 73 publications

References 55 publications

Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression

Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression

Dscam2 mediates axonal tiling in the Drosophila visual system

Direct control of neurogenesis by selector factors in the fly eye:regulation ofatonalby Ey and So

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