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Tetsuya Tabata

Publications and source records attributed to Tetsuya Tabata.

10 recordsLinked to original sources
PubMed2006

The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in the Drosophila visual system.

During development of the Drosophila visual center, photoreceptor cells extend their axons (R axons) to the lamina ganglion layer, and trigger proliferation and differentiation of synaptic partners (lamina neurons) by delivering the inductive signal Hedgehog (Hh). This inductive mechanism helps to establish an orderly arrangement of connections between the R axons and lamina neurons, termed a retinotopic map because it results in positioning the lamina neurons in close vicinity to the corresponding R axons. We found that the bHLH-PAS transcription factor Single-minded (Sim) is induced by Hh in the lamina neurons and is required for the association of lamina neurons with R axons. In sim mutant brains, lamina neurons undergo the first step of differentiation but fail to associate with R axons. As a result, lamina neurons are set aside from R axons. The data reveal a novel mechanism for regulation of the interaction between axons and neuronal cell bodies that establishes precise neuronal networks.

Animals↗
PubMed2005

DWnt4 regulates the dorsoventral specificity of retinal projections in the Drosophila melanogaster visual system.

In Drosophila melanogaster, the axons of retinal photoreceptor cells extend to the first optic ganglion, the lamina, forming a topographic representation. Here we show that DWnt4, a secreted protein of the Wnt family, is the ventral cue for the lamina. In DWnt4 mutants, ventral retinal axons misprojected to the dorsal lamina. DWnt4 was normally expressed in the ventral half of the developing lamina and DWnt4 protein was detected along ventral retinal axons. Dfrizzled2 and dishevelled, respectively, encode a receptor and a signaling molecule required for Wnt signaling. Mutations in both genes caused DWnt4-like defects, and both genes were autonomously required in the retina, suggesting a direct role of DWnt4 in retinal axon guidance. In contrast, iroquois homeobox genes are the dorsal cues for the retina. Dorsal axons accumulated DWnt4 and misprojected to the ventral lamina in iroquois mutants; the phenotype was suppressed in iroquois Dfrizzled2 mutants, suggesting that iroquois may attenuate the competence of Dfrizzled2 to respond to DWnt4.

Adaptor Proteins, Signal Transducing↗
PubMed2005

DPP signaling controls development of the lamina glia required for retinal axon targeting in the visual system of Drosophila.

The Drosophila visual system consists of the compound eyes and the optic ganglia in the brain. Among the eight photoreceptor (R) neurons, axons from the R1-R6 neurons stop between two layers of glial cells in the lamina, the most superficial ganglion in the optic lobe. Although it has been suggested that the lamina glia serve as intermediate targets of R axons, little is known about the mechanisms by which these cells develop. We show that DPP signaling plays a key role in this process. dpp is expressed at the margin of the lamina target region, where glial precursors reside. The generation of clones mutant for Medea, the DPP signal transducer, or inhibition of DPP signaling in this region resulted in defects in R neuron projection patterns and in the lamina morphology, which was caused by defects in the differentiation of the lamina glial cells. glial cells missing/glial cells deficient (gcm; also known as glide) is expressed shortly after glia precursors start to differentiate and migrate. Its expression depends on DPP; gcm is reduced or absent in dpp mutants or Medea clones, and ectopic activation of DPP signaling induces ectopic expression of gcm and REPO. In addition, R axon projections and lamina glia development were impaired by the expression of a dominant-negative form of gcm, suggesting that gcm indeed controls the differentiation of lamina glial cells. These results suggest that DPP signaling mediates the maturation of the lamina glia required for the correct R axon projection pattern by controlling the expression of gcm.

Animals↗
PubMed2005

[Morphogens].

Explore the source record for details and available documents.

Activins↗
PubMed2004

In vivo potentiation of human oestrogen receptor alpha by Cdk7-mediated phosphorylation.

Phosphorylation of the Ser(118) residue in the N-terminal A/B domain of the human oestrogen receptor alpha (hERalpha) by mitogen-activated protein kinase (MAPK), stimulated via growth factor signalling pathways, is known to potentiate ERalpha ligand-induced transactivation function. Besides MAPK, cyclin dependent kinase 7 (Cdk7) in the TFIIH complex has also been found to potentiate hERalpha transactivation in vitro through Ser(118) phosphorylation. To investigate an impact of Cdk7 on hERalpha transactivation in vivo, we assessed activity of hERalpha in a wild-type and cdk7 inactive mutant Drosophila that ectopically expressed hERalpha in the eye disc. Ectopic expression of the wild-type or mutant receptors, together with a green fluorescent protein (GFP) reporter gene, allowed us to demonstrate that hERalpha expressed in the fly tissues was transcriptionally functional and adequately responded to hERalpha ligands in the patterns similar to those observed in mammalian cells. Replacement of Ser(118) with alanine in hERalpha (S118A mutant) significantly reduced the ligand-induced hERalpha transactivation function. Importantly, while in cdk7 inactive mutant Drosophila the wild-type hERalpha exhibited reduced response to the ligand; levels of transactivation by the hERalpha S118A mutant were not affected in these inactive cdk7 mutant flies. Furthermore, phosphorylation of hERalpha at Ser(118) has been observed in vitro by both human and Drosophila Cdk7. Our findings demonstrate that Cdk7 is involved in regulation of the ligand-induced transactivation function of hERalphain vivo via Ser(118) phosphorylation.

Acetyltransferases↗
PubMed2004

Morphogens, their identification and regulation.

During the course of development, cells of many tissues differentiate according to the positional information that is set by the concentration gradients of morphogens. Morphogens are signaling molecules that emanate from a restricted region of a tissue and spread away from their source to form a concentration gradient. As the fate of each cell in the field depends on the concentration of the morphogen signal, the gradient prefigures the pattern of development. In this article, we describe how morphogens and their functions have been identified and analyzed, focusing on model systems that have been extensively studied.

Animals↗
PubMed2004

A novel genetic system for analysis of co-activators for the N-terminal transactivation function domain of the human androgen receptor.

Androgen receptor (hAR) regulates transcription of target genes in a ligand-dependent manner and recruits a number of co-activators for the ligand-induced transactivation via the N-terminal, activation function-1 (AF-1), and C-terminal, AF-2, transactivation domains. But the co-regulator functions on each of AR domains have not yet been fully understood. We have established a Drosophila transgenic system in which hAR and its deletion mutants are ectopically expressed in fly tissues together with an AR response element (ARE)-GFP reporter gene, and have confirmed that hAR was functional in ARE transactivation without affecting the expression of endogenous genes. We found that transcriptional activity of the hAR AF-1 domain was markedly reduced in Drosophila deficiency mutants of homologs for known mammalian co-activators of the AR ligand-dependent AF-2 domain. This suggests that hAR AF-1 recruits co-activators previously known only to interact with the AF-2 domain. Therefore, Drosophila with the hAR AF-1 transgene provides a relevant genetic system in which to uncover novel functions of vertebrate steroid hormone receptors and to screen for novel AF-1 co-regulators.

Animals↗
PubMed2003

Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans.

The signaling molecules Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg) function as morphogens and organize wing patterning in Drosophila. In the screen for mutations that alter the morphogen activity, we identified novel mutants of two Drosophila genes, sister of tout-velu (sotv) and brother of tout-velu (botv), and new alleles of tout-velu (ttv). The encoded proteins of these genes belong to an EXT family of proteins that have or are closely related to glycosyltransferase activities required for biosynthesis of heparan sulfate proteoglycans (HSPGs). Mutation in any of these genes impaired biosynthesis of HSPGs in vivo, indicating that, despite their structural similarity, they are not redundant in the HSPG biosynthesis. Protein levels and signaling activities of Hh, Dpp and Wg were reduced in the cells mutant for any of these EXT genes to a various degree, Wg signaling being the least sensitive. Moreover, all three morphogens were accumulated in the front of EXT mutant cells, suggesting that these morphogens require HSPGs to move efficiently. In contrast to previous reports that ttv is involved exclusively in Hh signaling, we found that ttv mutations also affected Dpp and Wg. These data led us to conclude that each of three EXT genes studied contribute to Hh, Dpp and Wg morphogen signaling. We propose that HSPGs facilitate the spreading of morphogens and therefore, function to generate morphogen concentration gradients.

Amino Acid Sequence↗
PubMed2002

Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset, neurodegenerative disorder affecting only males and is caused by expanded polyglutamine (polyQ) stretches in the N-terminal A/B domain of human androgen receptor (hAR). Although no overt phenotype was detected in adult fly eye photoreceptor neurons expressing mutant hAR (polyQ 52), ingestion of androgen or its known antagonists caused marked neurodegeneration with nuclear localization and structural alteration of the hAR mutant. Ligand-independent toxicity was detected with a truncated polyQ-expanded A/B domain alone, which was attenuated with cytosolic trapping by coexpression of the unliganded hAR E/F ligand binding domain. Thus, our findings suggest that the full binding of androgen to the polyQ-expanded hAR mutants leads to structural alteration with nuclear translocation that eventually results in the onset of SBMA in male patients.

Animals↗