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Ian Duncan - One of the best experts on this subject based on the ideXlab platform.
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Control of the spineless antennal enhancer: direct repression of antennal target genes by Antennapedia.
Developmental biology, 2010Co-Authors: Dianne M. Duncan, Paula Kiefel, Ian DuncanAbstract:It is currently thought that antennal target genes are activated in Drosophila by the combined action of Distal-less, Homothorax, and extradenticle, and that the Hox gene Antennapedia prevents activation of antennal genes in the leg by repressing Homothorax. To test these ideas, we analyze a 62 bp enhancer from the antennal gene spineless that is specific for the third antennal segment. This enhancer is activated by a tripartite complex of Distal-less, Homothorax, and Extradenticle. Surprisingly, Antennapedia represses the enhancer directly, at least in part by competing with Distal-less for binding. We show that Antennapedia is required in the leg only within a proximal ring that coexpresses Distal-less, Homothorax and Extradenticle. We conclude that the function of Antennapedia in the leg is not to repress Homothorax, as has been suggested, but to directly repress spineless and other antennal genes that would otherwise be activated within this ring.
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Regulation of the Drosophila distal antennal determinant spineless.
Developmental biology, 2006Co-Authors: Richard B. Emmons, Dianne M. Duncan, Ian DuncanAbstract:The transformation of antenna to leg is a classical model for understanding segmental fate decisions in Drosophila. The spineless (ss) gene encodes a bHLH-PAS transcription factor that plays a key role in specifying the identity of distal antennal segments. In this report, we identify the antennal disc enhancer of ss and then use enhancer-lacZ reporters to work out how ss antennal expression is regulated. The antennal determinants Distal-less (Dll) and Homothorax (hth) are key activators of the antennal enhancer. Dll is required continuously and, when present at elevated levels, can activate the enhancer in regions devoid of hth expression. In contrast, Homothorax (hth) is required only transiently both for activation of the enhancer and for specification of the aristal portion of the antenna. The antennal enhancer is repressed by cut, which determines its proximal limit of expression, and by ectopic Antennapedia (Antp). Repression by Antp is not mediated by hth, suggesting that ss may be a direct target of Antp. Finally, we show that ss+ is not a purely passive target of its regulators: ss+ partially represses hth in the third antennal segment and lies upstream of Dll in the development of the maxillary palp primordia.
Fernando Casares - One of the best experts on this subject based on the ideXlab platform.
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The retinal determination gene dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex
Development (Cambridge England), 2015Co-Authors: Catarina Brás-pereira, Fernando Casares, Florence JanodyAbstract:The Drosophila transcriptional co-activator protein Yorkie and its vertebrate orthologs YAP and TAZ are potent oncogenes, whose activity is normally kept in check by the upstream Hippo kinase module. Upon its translocation into the nucleus, Yorkie forms complexes with several tissue-specific DNA-binding partners, which help to define the tissue-specific target genes of Yorkie. In the progenitor cells of the eye imaginal disc, the DNA-binding transcription factor Homothorax is required for Yorkie-promoted proliferation and survival through regulation of the bantam microRNA (miRNA). The transit from proliferating progenitors to cell cycle quiescent precursors is associated with the progressive loss of Homothorax and gain of Dachshund, a nuclear protein related to the Sno/Ski family of co-repressors. We have identified Dachshund as an inhibitor of Homothorax-Yorkie-mediated cell proliferation. Loss of dachshund induces Yorkie-dependent tissue overgrowth. Conversely, overexpressing dachshund inhibits tissue growth, prevents Yorkie or Homothorax-mediated cell proliferation of disc epithelia and restricts the transcriptional activity of the Yorkie-Homothorax complex on the bantam enhancer in Drosophila cells. In addition, Dachshund collaborates with the Decapentaplegic receptor Thickveins to repress Homothorax and Cyclin B expression in quiescent precursors. The antagonistic roles of Homothorax and Dachshund in Yorkie activity, together with their mutual repression, ensure that progenitor and precursor cells are under distinct proliferation regimes. Based on the crucial role of the human dachshund homolog DACH1 in tumorigenesis, our work suggests that DACH1 might prevent cellular transformation by limiting the oncogenic activity of YAP and/or TAZ.
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Homothorax and iroquois-C genes are required for the establishment of territories within the developing eye disc.
Mechanisms of development, 2000Co-Authors: Franck Pichaud, Fernando CasaresAbstract:In Drosophila the eye-antennal disc gives rise to most adult structures of the fly's head. Yet the molecular basis for its regionalization during development is poorly understood. Here we show that Homothorax is required early during development for normal eye development and is necessary for the formation of the ventral head capsule. In the ventral region of the disc only, Homothorax and wingless are involved in a positive feedback loop necessary to restrict eye formation. Homothorax is able to prevent the initiation and progression of the morphogenetic furrow without inducing wingless, which points to Homothorax as a key negative regulator of eye development. In addition, we show that the iroquois-complex genes are required for dorsal head development antagonizing the function of Homothorax in this region of the disc.
Florence Janody - One of the best experts on this subject based on the ideXlab platform.
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The retinal determination gene dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex
Development (Cambridge England), 2015Co-Authors: Catarina Brás-pereira, Fernando Casares, Florence JanodyAbstract:The Drosophila transcriptional co-activator protein Yorkie and its vertebrate orthologs YAP and TAZ are potent oncogenes, whose activity is normally kept in check by the upstream Hippo kinase module. Upon its translocation into the nucleus, Yorkie forms complexes with several tissue-specific DNA-binding partners, which help to define the tissue-specific target genes of Yorkie. In the progenitor cells of the eye imaginal disc, the DNA-binding transcription factor Homothorax is required for Yorkie-promoted proliferation and survival through regulation of the bantam microRNA (miRNA). The transit from proliferating progenitors to cell cycle quiescent precursors is associated with the progressive loss of Homothorax and gain of Dachshund, a nuclear protein related to the Sno/Ski family of co-repressors. We have identified Dachshund as an inhibitor of Homothorax-Yorkie-mediated cell proliferation. Loss of dachshund induces Yorkie-dependent tissue overgrowth. Conversely, overexpressing dachshund inhibits tissue growth, prevents Yorkie or Homothorax-mediated cell proliferation of disc epithelia and restricts the transcriptional activity of the Yorkie-Homothorax complex on the bantam enhancer in Drosophila cells. In addition, Dachshund collaborates with the Decapentaplegic receptor Thickveins to repress Homothorax and Cyclin B expression in quiescent precursors. The antagonistic roles of Homothorax and Dachshund in Yorkie activity, together with their mutual repression, ensure that progenitor and precursor cells are under distinct proliferation regimes. Based on the crucial role of the human dachshund homolog DACH1 in tumorigenesis, our work suggests that DACH1 might prevent cellular transformation by limiting the oncogenic activity of YAP and/or TAZ.
Stephen M. Cohen - One of the best experts on this subject based on the ideXlab platform.
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Limb development: getting down to the ground state.
Current biology : CB, 2001Co-Authors: B. Starling Emerald, Stephen M. CohenAbstract:In 1935, Snodgrass proposed that the evolutionary ground state of arthropod limbs consisted of two segments. Recent genetic studies on the Antennapedia and Homothorax genes of Drosophila raise questions about the nature of this ground state appendage.
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Proximal distal axis formation in the Drosophila leg: distinct functions of teashirt and Homothorax in the proximal leg.
Mechanisms of Development, 2000Co-Authors: Stephen M. CohenAbstract:The proximal distal axis of the Drosophila leg is patterned by expression of a number of transcription factors in discrete domains along the axis. The homeodomain protein Homothorax and the zinc-finger protein Teashirt are broadly coexpressed in the presumptive body wall and proximal leg segments. Homothorax has been implicated in forming a boundary between proximal and distal segments of the leg. We present evidence that Teashirt is required for the formation of proximal leg segments, but has no role in boundary formation.
Grace Panganiban - One of the best experts on this subject based on the ideXlab platform.
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Distal-less and Homothorax regulate multiple targets to pattern the Drosophila antenna
Development (Cambridge England), 2002Co-Authors: P. D. Si Dong, Jennifer Scholz Dicks, Grace PanganibanAbstract:The Drosophila antenna is a highly derived appendage required for a variety of sensory functions including olfaction and audition. To investigate how this complex structure is patterned, we examine the specific functions of genes required for antenna development. The nuclear factors, Homothorax, Distal-less and Spineless, are each required for particular aspects of antennal fate. Coexpression of Homothorax, necessary for nuclear localization of its ubiquitously expressed partner Extradenticle, with Distal-less is required to establish antenna fate. Here we test which antenna patterning genes are targets of Homothorax, Distal-less and/or Spineless. We report that the antennal expression of dachshund, atonal, spalt, and cut requires Homothorax and/or Distal-less, but not Spineless. We conclude that Distal-less and Homothorax specify antenna fates via regulation of multiple genes. We also report for the first time phenotypic consequences of losing either dachshund or spalt and spalt-related from the antenna. We find that dachshund and spalt/spalt-related are essential for proper joint formation between particular antennal segments. Furthermore, the spalt/spalt-related null antennae are defective in hearing. Hearing defects are also associated with the human diseases Split Hand/Split Foot Malformation and Townes-Brocks Syndrome, which are linked to human homologs of Distal-less and spalt, respectively. We therefore propose that there are significant genetic similarities between the auditory organs of humans and flies.