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Gerold Schubiger - One of the best experts on this subject based on the ideXlab platform.
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developmental analysis and squamous morphogenesis of the peripodial epithelium in drosophila Imaginal Discs
Development, 2005Co-Authors: Kimberly D Mcclure, Gerold SchubigerAbstract:Imaginal Discs of Drosophila provide an excellent system with which to study morphogenesis, pattern formation and cell proliferation in an epithelium. Discs are sac-like in structure and are composed of two epithelial layers: an upper peripodial epithelium and lower disc proper. Although development of the disc proper has been studied extensively in terms of cell proliferation, cell signaling mechanisms and pattern formation, little is known about these same processes in the peripodial epithelium. We address this topic by focusing on morphogenesis, compartmental organization, proliferation and cell lineage of the PE in wing, second thoracic leg (T2) and eye Discs. We show that a subset of peripodial cells in different Imaginal Discs undergo a cuboidal-to-squamous cell shape change at distinct larval stages. We find that this shape change requires both Hedgehog and Decapentapelagic, but not Wingless, signaling. Additionally, squamous morphogenesis shifts the anteroposterior (AP) compartment boundary in the peripodial epithelium relative to the stationary AP boundary in the disc proper. Finally, by lineage tracing cells in the PE, we surprisingly find that peripodial cells are displaced into the disc proper during larval development and this movement leads to Ubx repression.
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Lumenal transmission of decapentaplegic in Drosophila Imaginal Discs.
Developmental Cell, 2002Co-Authors: Matthew C. Gibson, Dara A. Lehman, Gerold SchubigerAbstract:Drosophila Imaginal Discs are sac-like appendage primordia comprising apposed peripodial and columnar cell layers. Cell survival in disc columnar epithelia requires the secreted signal Decapentaplegic (DPP), which also acts as a gradient morphogen during pattern formation. The distribution mechanism by which secreted DPP mediates global cell survival and graded patterning is poorly understood. Here we report detection of DPP in the lumenal cavity between apposed peripodial and columnar cell layers of both wing and eye Discs. We show that peripodial cell survival hinges upon DPP signal reception and implicate DPP-dependent viability of the peripodial epithelium in growth of the entire disc. These results are consistent with lumenal transmission of the DPP survival signal during Imaginal disc development.
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peripodial cells regulate proliferation and patterning of drosophila Imaginal Discs
Cell, 2000Co-Authors: Matthew C. Gibson, Gerold SchubigerAbstract:Cells employ a diverse array of signaling mechanisms to establish spatial patterns during development. Nowhere is this better understood than in Drosophila, where the limbs and eyes arise from discrete epithelial sacs called Imaginal Discs. Molecular-genetic analyses of pattern formation have generally treated Discs as single epithelial sheets. Anatomically, however, Discs comprise a columnar cell monolayer covered by a squamous epithelium known as the peripodial membrane. Here we demonstrate that during development, peripodial cells signal to disc columnar cells via microtubule-based apical extensions. Ablation and targeted gene misexpression experiments demonstrate that peripodial cell signaling contributes to growth control and pattern formation in the eye and wing primordia. These findings challenge the traditional view of Discs as monolayers and provide foundational evidence for peripodial cell function in Drosophila appendage development.
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Cell determination and transdetermination in Drosophila Imaginal Discs.
Current Topics in Developmental Biology, 1998Co-Authors: Lisa Maves, Gerold SchubigerAbstract:Drosophila Imaginal Discs, the precursors of the adult fly appendages, are an important system for studying mechanisms of cell determination. How the different Imaginal Discs acquire and maintain their appendage-specific determined states are problems that have been addressed using experimental embryology as well as genetic and molecular approaches. Here we discuss the concept of cell determination and describe what is known about how determination is established and maintained in Imaginal disc cells. The phenomenon of Imaginal disc transdetermination, originally discovered in the 1960s, has remained an intriguing problem for understanding Imaginal disc cell determination. We review the topic of Imaginal disc transdetermination and describe how recent results from molecular genetic approaches have provided new insights into Imaginal disc transdetermination and determination. We also discuss how an understanding of Imaginal disc transdetermination can aid our understanding of parallel phenomena in other organisms, including human metaplasias.
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ectopic expression of wingless in Imaginal Discs interferes with decapentaplegic expression and alters cell determination
Development, 1996Co-Authors: Laura A Johnston, Gerold SchubigerAbstract:We have expressed the segment polarity gene wingless (wg) ectopically in Imaginal Discs to examine its regulation of both ventral patterning and transdetermination. By experimentally manipulating the amount of Wg protein, we show that different thresholds of Wg activity elicit different outcomes, which are mediated by regulation of decapentaplegic (dpp) expression and result in alterations in the expression of homeotic genes. A high level of Wg activity leads to loss of all dorsal pattern elements and the formation of a complete complement of ventral pattern elements on the dorsal side of legs, and is correlated with repression of dpp expression. wg expression in dorsal cells of each disc also leads to dose-dependent transdetermination in those cells in homologous Discs such as the labial, antennal and leg, but not in cells of dorsally located Discs. When dpp expression is repressed by high levels of Wg, transdetermination does not occur, confirming that dpp participates with wg to induce transdetermination. These and other experiments suggest that dorsal expression of wg alters disc patterning and disc cell determination by modulating the expression of dpp. The dose-dependent effects of wg on dpp expression, ventralization of dorsal cells and transdetermination support a model in which wg functions as a morphogen in Imaginal Discs.
Ginés Morata - One of the best experts on this subject based on the ideXlab platform.
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Cell competition and tumorigenesis in the Imaginal Discs of Drosophila.
Seminars in Cancer Biology, 2020Co-Authors: Ginés Morata, Manuel CallejaAbstract:Abstract Cancer is a major health issue and the object of investigations in thousands of laboratories all over the world. Most of cancer research is being carried out in in vitro systems or in animal models, generally mice or rats. However, the discovery of the high degree of genetic identity among metazoans has prompted investigation in organisms like Drosophila, on the idea that the genetic basis of cancer in flies and humans may have many aspects in common. Moreover, the sophisticated genetic methodology of Drosophila offers operational advantages and allows experimental approaches inaccessible in other species. Cell competition is a cell-quality control process that aims to identifying and subsequently removing cells within animal tissues that are unfit, abnormal or aberrant, and that may compromise the fitness or the viability of the organism. It was originally described in Drosophila Imaginal Discs but later work has shown it occurs in mammalian tissues where it fulfils similar roles. One aspect of the surveillance role of cell competition is to eliminate oncogenic cells that may appear during development or the life of an organism. In this review we have focussed on the work on Drosophila Imaginal Discs relating cell competition and tumorigenic processes. We briefly discuss related work in mammalian tissues.
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Regenerative response of different regions of Drosophila Imaginal Discs
The International Journal of Developmental Biology, 2018Co-Authors: Raquel Martín, Ginés MorataAbstract:Thanks to the introduction of new methods to induce massive damage under controlled conditions, much information about regeneration in Drosophila Imaginal Discs has accumulated in recent years. In this review, we discuss results concerning primarily the wing disc, putting emphasis on the different regenerative responses of the wing appendage, which exhibits a robust regenerative potential, and the trunk region, the notum, which regenerates very poorly. The wing disc may be a paradigm of a tissue in which a common original lineage generates cells with distinct regenerative potential. We argue that a key factor in those differences is the activity of the Jun N-terminal Kinase (JNK) pathway, which functions differently in the appendage and the body trunk.
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The role of buttonhead and Sp1 in the development of the ventral Imaginal Discs of Drosophila.
Development, 2003Co-Authors: Carlos Estella, Manuel Calleja, Gabrielle Rieckhof, Ginés MorataAbstract:The related genes buttonhead ( btd ) and Drosophila Sp1 (the Drosophila homologue of the human SP1 gene) encode zinc-finger transcription factors known to play a developmental role in the formation of the Drosophila head segments and the mechanosensory larval organs. We report a novel function of btd and Sp1 : they induce the formation and are required for the growth of the ventral Imaginal Discs. They act as activators of the headcase ( hdc ) and Distal-less ( Dll ) genes, which allocate the cells of the disc primordia. The requirement for btd and Sp1 persists during the development of ventral Discs: inactivation by RNA interference results in a strong reduction of the size of legs and antennae. Ectopic expression of btd in the dorsal Imaginal Discs (eyes, wings and halteres) results in the formation of the corresponding ventral structures (antennae and legs). However, these structures are not patterned by the morphogenetic signals present in the dorsal Discs; the cells expressing btd generate their own signalling system, including the establishment of a sharp boundary of engrailed expression, and the local activation of the wingless and decapentaplegic genes. Thus, the Btd product has the capacity to induce the activity of the entire genetic network necessary for ventral Imaginal Discs development. We propose that this property is a reflection of the initial function of the btd/Sp1 genes that consists of establishing the fate of the ventral disc primordia and determining their pattern and growth.
Juan F. Santarén - One of the best experts on this subject based on the ideXlab platform.
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Constitutive expression of heat shock protein p23 correlates with proneural territories in Imaginal Discs of Drosophila melanogaster
PROTEOMICS, 2005Co-Authors: Jana Alonso, Javier M. Rodríguez, Luis Alberto Baena-lopez, Maria Teresa Alonso, Juan F. SantarénAbstract:2-DE followed by MALDI-TOF was used to purify and identify a Drosophila protein (catalogued as SSP 6002) that showed marked differences in the level of expression in the different Imaginal Discs of third instar larvae. Fingerprinting showed that the spot of interest was the heat shock 23 polypeptide (hsp23). We characterized the kinetics of its induction by heat shock in wing Imaginal Discs and raised an antiserum against the denatured protein, which recognizes a single unphosphorylated spot on 2-D gels. The difference in its expression in Discs was corroborated by analyzing its level in the Imaginal Discs of postbithorax mutants. We also investigated the developmental expression of hsp23 in Imaginal Discs with antiserum raised against the native protein. Its spatial and temporal pattern of expression is related to the proneural territories and maintained even under heat shock conditions. In addition, its pattern of expression is regulated by transcription factors and signaling pathways (notch and epidermal growth factor receptor) involved in proneural specification.
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Proteomic analysis of the wing Imaginal Discs of Drosophila melanogaster.
PROTEOMICS, 2004Co-Authors: Jana Alonso, Juan F. SantarénAbstract:We have combined high-resolution two-dimensional (2-D) gel electrophoresis and mass spectrometry with the aim of identifying proteins represented in the 2-D gel database of the wing Imaginal Discs of Drosophila melanogaster. First, we obtained a high-resolution 2-D gel pattern of [ 35 S]methionine + [ 35 S]cysteine-labeled polypeptides of Schneider cells, a permanent cell line of Drosophila embryonic origin, and compared it with the standard pattern of polypeptides of the wing Imaginal disc. These studies reveal qualitative and quantitative differences between the two samples, but have more than 600 polypeptides in common. Second, we carried out preparative 2-D polyacrylamide gel electrophoresis using Schneider cells mixed with radioactively labeled wing Imaginal Discs in order to isolate some of the shared polypeptides and characterize them by matrix-assisted laser desorption/ionization-time of flight MALDI-TOF analysis. Using this strategy we identified 100 shared proteins represented in the database, and in each case confirmed their identity by MALDI-TOF/TOF analysis.
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Patterns of protein synthesis in the Imaginal Discs of Drosophila melanogaster: a comparison between different Discs and stages.
Roux's Archives of Developmental Biology, 1993Co-Authors: Juan F. Santarén, Rosa Assiego, Antonio García-bellidoAbstract:High-resolution two dimensional gel electrophoresis has been used to study the patterns of protein synthesis in Imaginal Discs of Drosophila melanogaster. In this paper we first compare the patterns of protein synthesis in wing, haltere, leg 1, leg 2, leg 3 and eye antenna Imaginal Discs of late third instar larvae. We have detected only quantitative changes: differences in 17 proteins among the different Imaginal Discs. In addition, we have analysed the variations in pattern of proteins in the wing disc of the last larval stage and early pupae as well as in wing Discs cultured in vivo for 6 days. Variations in these patterns affect more than 20% of the proteins and involve both qualitative and quantitative changes. Some of the changes may correspond to protein phosphorylation. Correlations of these changes between Discs and through development are also discussed.
Denise Busson - One of the best experts on this subject based on the ideXlab platform.
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modulation of hedgehog target gene expression by the fused serine threonine kinase in wing Imaginal Discs
Mechanisms of Development, 1998Co-Authors: Georges Alves, Bernadette Limbourgbouchon, Herve Tricoire, Jeanine Brissardzahraoui, Claudie Lamourisnard, Denise BussonAbstract:The Fused (Fu) serine–threonine kinase and the Suppressor of fused (Su(fu)) product are part of the Hedgehog (Hh) signalling pathway both in embryos and in Imaginal Discs. In wing Imaginal Discs, the Hh signal induces Cubitus interruptus (Ci) accumulation and activates patched (ptc) and decapentaplegic (dpp) expression along the anterior/posterior (A/P) boundary. In this paper, we have examined the role of the Fu and Su(fu) proteins in the regulation of Hh target gene expression in wing Imaginal Discs, by using different classes of fu alleles and an amorphic Su(fu) mutation. We show that, at the A/P boundary, Fu kinase activity is involved in the maintenance of high ptc expression and in the induction of late anterior engrailed (en) expression. These combined effects can account for the modulation of Ci accumulation and for the precise localization of the Dpp morphogen stripe. In contrast, in more anterior cells which do not receive Hh signal, we show that Fu plays a role independent of its kinase function in the regulation of Ci accumulation. In these cells, Fu may be involved in the stabilization of a large protein complex which is probably responsible for the regulation of Ci cleavage and/or targeting to nucleus. We propose that the Fused function is necessary for the activation of full-length Ci and counteracts the negative Su(fu) effect on the pathway, leading to en, ptc and dpp expression.
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Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing Imaginal Discs
Mechanisms of Development, 1998Co-Authors: Georges Alves, Herve Tricoire, Bernadette Limbourg-bouchon, Jeanine Brissard-zahraoui, Claudie Lamour-isnard, Denise BussonAbstract:The Fused (Fu) serine–threonine kinase and the Suppressor of fused (Su(fu)) product are part of the Hedgehog (Hh) signalling pathway both in embryos and in Imaginal Discs. In wing Imaginal Discs, the Hh signal induces Cubitus interruptus (Ci) accumulation and activates patched (ptc) and decapentaplegic (dpp) expression along the anterior/posterior (A/P) boundary. In this paper, we have examined the role of the Fu and Su(fu) proteins in the regulation of Hh target gene expression in wing Imaginal Discs, by using different classes of fu alleles and an amorphic Su(fu) mutation. We show that, at the A/P boundary, Fu kinase activity is involved in the maintenance of high ptc expression and in the induction of late anterior engrailed (en) expression. These combined effects can account for the modulation of Ci accumulation and for the precise localization of the Dpp morphogen stripe. In contrast, in more anterior cells which do not receive Hh signal, we show that Fu plays a role independent of its kinase function in the regulation of Ci accumulation. In these cells, Fu may be involved in the stabilization of a large protein complex which is probably responsible for the regulation of Ci cleavage and/or targeting to nucleus. We propose that the Fused function is necessary for the activation of full-length Ci and counteracts the negative Su(fu) effect on the pathway, leading to en, ptc and dpp expression. î 1998 Elsevier Science Ireland Ltd. All rights reserved
Jana Alonso - One of the best experts on this subject based on the ideXlab platform.
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Constitutive expression of heat shock protein p23 correlates with proneural territories in Imaginal Discs of Drosophila melanogaster
PROTEOMICS, 2005Co-Authors: Jana Alonso, Javier M. Rodríguez, Luis Alberto Baena-lopez, Maria Teresa Alonso, Juan F. SantarénAbstract:2-DE followed by MALDI-TOF was used to purify and identify a Drosophila protein (catalogued as SSP 6002) that showed marked differences in the level of expression in the different Imaginal Discs of third instar larvae. Fingerprinting showed that the spot of interest was the heat shock 23 polypeptide (hsp23). We characterized the kinetics of its induction by heat shock in wing Imaginal Discs and raised an antiserum against the denatured protein, which recognizes a single unphosphorylated spot on 2-D gels. The difference in its expression in Discs was corroborated by analyzing its level in the Imaginal Discs of postbithorax mutants. We also investigated the developmental expression of hsp23 in Imaginal Discs with antiserum raised against the native protein. Its spatial and temporal pattern of expression is related to the proneural territories and maintained even under heat shock conditions. In addition, its pattern of expression is regulated by transcription factors and signaling pathways (notch and epidermal growth factor receptor) involved in proneural specification.
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Proteomic analysis of the wing Imaginal Discs of Drosophila melanogaster.
PROTEOMICS, 2004Co-Authors: Jana Alonso, Juan F. SantarénAbstract:We have combined high-resolution two-dimensional (2-D) gel electrophoresis and mass spectrometry with the aim of identifying proteins represented in the 2-D gel database of the wing Imaginal Discs of Drosophila melanogaster. First, we obtained a high-resolution 2-D gel pattern of [ 35 S]methionine + [ 35 S]cysteine-labeled polypeptides of Schneider cells, a permanent cell line of Drosophila embryonic origin, and compared it with the standard pattern of polypeptides of the wing Imaginal disc. These studies reveal qualitative and quantitative differences between the two samples, but have more than 600 polypeptides in common. Second, we carried out preparative 2-D polyacrylamide gel electrophoresis using Schneider cells mixed with radioactively labeled wing Imaginal Discs in order to isolate some of the shared polypeptides and characterize them by matrix-assisted laser desorption/ionization-time of flight MALDI-TOF analysis. Using this strategy we identified 100 shared proteins represented in the database, and in each case confirmed their identity by MALDI-TOF/TOF analysis.