The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Pat Simpson - One of the best experts on this subject based on the ideXlab platform.
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Conservation of upstream regulators of scute on the Notum of cyclorraphous Diptera
Development Genes and Evolution, 2006Co-Authors: Pat Simpson, Morag Lewis, Joanna RichardsonAbstract:Bristles on the Notum of many cyclorraphous flies are arranged into species-specific stereotyped patterns. Differences in the spatial expression of the proneural gene scute correlate with the positions of bristles in those species looked at so far. However, the examination of a number of genes encoding trans -regulatory factors, such as pannier , stripe , u-shaped , caupolican and wingless , indicates that they are expressed in conserved domains on the prospective Notum. This suggests that the function of a trans -regulatory network of genes is relatively unchanged in derived Diptera, and that many differences are likely to be due to changes in cis -regulatory sequences of scute . In contrast, in Anopheles gambiae , a basal species with no stereotyped bristle pattern, the expression patterns of pannier and wingless are not conserved, and expression of AgASH , the Anopheles proneural gene, does not correlate in a similar manner with the bristle pattern. We discuss the possibility that independently acting cis -regulatory sequences at the scute locus may have arisen in the lineage giving rise to cyclorraphous flies.
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A conserved trans-regulatory landscape for scute expression on the Notum of cyclorraphous Diptera
Development Genes and Evolution, 2006Co-Authors: Joanna Richardson, Pat SimpsonAbstract:Bristles on the Notum of many cyclorraphous flies are arranged into species-specific stereotyped patterns. The positions of bristles correlate with differences in the spatial expression of the scute (sc) gene in those species examined so far. However, a major upstream activator of scute , Pannier (Pnr), is expressed in a conserved domain over the entire medial Notum. Here we examine the expression patterns in Calliphora vicina of stripe ( sr ), u-shaped ( ush ), caupolican ( caup ) and wingless ( wg ), genes known to modify the activity of Pnr or to act downstream of Pnr in Drosophila . We find that, with minor differences, their expression patterns are conserved. This suggests that the function of a trans -regulatory network of genes is relatively unchanged in derived Diptera and that many differences are likely to be due to changes in cis -regulatory sequences of scute .
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the expression of pannier and achaete scute homologues in a mosquito suggests an ancient role of pannier as a selector gene in the regulation of the dorsal body pattern
Development, 2002Co-Authors: Corinna Wulbeck, Pat SimpsonAbstract:The Drosophila gene pannier ( pnr ) has recently been assigned to a new class of selector genes (Calleja, M., Herranz, H., Estella, C., Casal, J., Lawrence, P., Simpson, P. and Morata, G. (2000). Development 127, 3971-3980; (Mann, R. S. and Morata, G. (2000). Annu. Rev. Cell Dev. Biol. 16, 243-271). It specifies pattern in the dorsal body. On the dorsal Notum it is expressed in a broad medial domain and directly regulates transcription of the achaete-scute ( ac-sc ) genes driving their expression in small discrete clusters within this domain at the sites of each future bristle. This spatial resolution is achieved through modulation of Pnr activity by specific co-factors and by a number of discrete cis -regulatory enhancers in the ac-sc gene complex. We have isolated homologues of pnr and ac-sc in Anopheles gambiae , a basal species of Diptera that diverged from Drosophila melanogaster ( Dm ) about 200 million years ago, and examined their expression patterns. We found that an ac-sc homologue of Anopheles , Ag-ASH , is expressed on the dorsal medial Notum at the sites where sensory organs emerge in several domains that are identical to those of the pnr homologue, Ag-pnr . This suggests that activation of Ag-ASH by Ag-Pnr has been conserved. Indeed, when expressed in Drosophila , Ag-pnr is able to mimic the effects of ectopic expression of Dm-pnr and induce ectopic bristles. These results are discussed in the context of the gene duplication events and the acquisition of a modular promoter, that may have occurred at different times in the lineage leading to derived species such as Drosophila . The bristle pattern of Anopheles correlates in a novel fashion with the expression domains of Ag-pnr/Ag-ASH . While precursors for the sensory scales can arise anywhere within the expression domains, bristle precursors arise exclusively along the borders. This points to the existence of specific positional information along the borders, and suggests that Ag-pnr specifies pattern in the medial, dorsal Notum, as in Drosophila , but via a different mechanism.
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how to pattern an epithelium lessons from achaete scute regulation on the Notum of drosophila
Gene, 2002Co-Authors: Manuel Calleja, Gines Morata, Olivier Renaud, Kazuya Usui, Daniela Pistillo, Pat SimpsonAbstract:The Notum of Drosophila is a good model system for the study of two-dimensional pattern formation. Attention has mainly focused on the regulation of the spatial expression of the genes of the achaete-scute complex (AS-C) that results in a stereotyped bristle pattern. Expression of AS-C genes has traditionally been viewed as a consequence of the activity of a group of factors that constitute a prepattern [Stern, 1954. Am. Sci. 42, 213]. The prepattern is thought to be composed of a mosaic of transcription factors that act in combination, through discrete cis-regulatory sequences, to activate expression of genes of the AS-C in small clusters of cells at the sites of each future bristle. Recent results challenge this view and suggest a hierarchy of activity amongst prepattern genes. It is suggested that in the medial Notum, the selector-like gene pannier regulates the entire pattern, and is the only factor to directly activate AS-C genes. Other factors may play subsidiary roles. On the lateral Notum genes of the iroquois complex appear to regulate the lateral pattern. Regulation of pannier and iroquois depends upon the signalling molecule Decapentaplegic. The majority of genes are expressed in either longitudinal or transverse domains on the Notum and we discuss the possibility that pattern formation may rely on these two axial coordinates. We also discuss preliminary results suggesting that prepattern factors also regulate genes required for other, little studied, aspects of notal morphology, such as the muscle attachment sites and pigment distribution. Thus there may be a common prepattern for the entire structure.
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expression of achaete scute homologues in discrete proneural clusters on the developing Notum of the medfly ceratitis capitata suggests a common origin for the stereotyped bristle patterns of higher diptera
Development, 2000Co-Authors: Corinna Wulbeck, Pat SimpsonAbstract:The stereotyped positioning of sensory bristles in Drosophila has been shown to result from complex spatiotemporal regulation of the proneural achaete-scute genes, that relies on an array of cis-regulatory elements and spatially restricted transcriptional activators such as Pannier. Other species of derived schizophoran Diptera have equally stereotyped, but different, bristle patterns. Divergence of bristle patterns could arise from changes in the expression pattern of proneural genes, resulting from evolution of the cis-regulatory sequences and/or altered expression patterns of transcriptional regulators. Here we describe the isolation of achaete-scute homologues in Ceratitis capitata, a species of acalyptrate Schizophora whose bristle pattern differs slightly from that of Drosophila. At least three genes, scute, lethal of scute and asense have been conserved, thus demonstrating that gene duplication within the achaete-scute complex preceded the separation of the families Drosophilidae and Tephritidae, whose common ancestor goes back more than 100 million years. The expression patterns of these genes provide evidence for conservation of many cis-regulatory elements as well as a common origin for the stereotyped patterns seen on the scutum of many Schizophora. Some aspects of the transcriptional regulation have changed, however, and correlate in the Notum with differences in the bristle pattern. The Ceratitis pannier gene was isolated and displays a conserved expression domain in the Notum.
Gary Struhl - One of the best experts on this subject based on the ideXlab platform.
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subdivision of the drosophila wing imaginal disc by egfr mediated signaling
Development, 2002Co-Authors: Myriam Zecca, Gary StruhlAbstract:Growth and patterning of the Drosophila wing imaginal disc depends on its subdivision into dorsoventral (DV) compartments and limb (wing) and body wall (Notum) primordia. We present evidence that both the DV and wing-Notum subdivisions are specified by activation of the Drosophila Epidermal Growth Factor Receptor (EGFR). We show that EGFR signaling is necessary and sufficient to activate apterous (ap) expression, thereby segregating the wing disc into D (ap-ON) and V (ap-OFF) compartments. Similarly, we demonstrate that EGFR signaling directs the expression of Iroquois Complex (Iro-C) genes in prospective Notum cells, rendering them distinct from, and immiscible with, neighboring wing cells. However, EGFR signaling acts only early in development to heritably activate ap, whereas it is required persistently during subsequent development to maintain Iro-C gene expression. Hence, as the disc grows, the DV compartment boundary can shift ventrally, beyond the range of the instructive EGFR signal(s), in contrast to the Notum-wing boundary, which continues to be defined by EGFR input.
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control of growth and patterning of the drosophila wing imaginal disc by egfr mediated signaling
Development, 2002Co-Authors: Myriam Zecca, Gary StruhlAbstract:The subdivision of the Drosophila wing imaginal disc into dorsoventral (DV) compartments and limb-body wall (wing-Notum) primordia depends on Epidermal Growth Factor Receptor (EGFR) signaling, which heritably activates apterous (ap) in D compartment cells and maintains Iroquois Complex (Iro-C) gene expression in prospective Notum cells. We examine the source, identity and mode of action of the EGFR ligand(s) that specify these subdivisions. Of the three known ligands for the Drosophila EGFR, only Vein (Vn), but not Spitz or Gurken, is required for wing disc development. We show that Vn activity is required specifically in the dorsoproximal region of the wing disc for ap and Iro-C gene expression. However, ectopic expression of Vn in other locations does not reorganize ap or Iro-C gene expression. Hence, Vn appears to play a permissive rather than an instructive role in organizing the DV and wing-Notum segregations, implying the existance of other localized factors that control where Vn-EGFR signaling is effective. After ap is heritably activated, the level of EGFR activity declines in D compartment cells as they proliferate and move ventrally, away from the source of the instructive ligand. We present evidence that this reduction is necessary for D and V compartment cells to interact along the compartment boundary to induce signals, like Wingless (Wg), which organize the subsequent growth and differentiation of the wing primordium.
Christine Damblychaudiere - One of the best experts on this subject based on the ideXlab platform.
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the iroquois complex controls the somatotopy of drosophila Notum mechanosensory projections
Development, 1998Co-Authors: N Grillenzoni, Christine Damblychaudiere, J Van Helden, Alain GhysenAbstract:Sensory neurons can establish topologically ordered projections in the central nervous system, thereby building an internal representation of the external world. We analyze how this ordering is genetically controlled in Drosophila, using as a model system the neurons that innervate the mechanosensory bristles on the back of the fly (the Notum). Sensory neurons innervating the medially located bristles send an axonal branch that crosses the central nervous system midline, defining a 'medial' identity, while the ones that innervate the lateral bristles send no such branch, defining a 'lateral' identity. We analyze the role of the proneural genes achaete and scute, which are involved in the formation of the medial and lateral bristles, and we show that they have no effect on the 'medial' and 'lateral' identities of the neurons. We also analyze the role of the prepattern genes araucan and caupolican, two members of the iroquois gene complex which are required for the expression of achaete and scute in the lateral region of the Notum, and we show that their expression is responsible for the 'lateral' identity of the projection.
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iroquois a prepattern gene that controls the formation of bristles on the thorax of drosophila
Mechanisms of Development, 1996Co-Authors: Luc Leyns, Jose Luis Gomezskarmeta, Christine DamblychaudiereAbstract:We have isolated a Drosophila mutant where the lateral parts of the Notum are completely naked, leaving unaffected a median stripe of hairs. This mutation, iroquois (iro), defines a new gene which maps at 69D. We show that, in the presumptive lateral Notum of mutant discs, sense organ precursor cells fail to form and the proneural gene scute is not expressed. The expression of a reporter gene inserted near iro suggests that iro itself is massively expressed in this region of the disc. We propose that iro is a prepattern gene essential to activate the expression of scute in the regions of the disc that will form the lateral Notum.
Sofia Moverareskrtic - One of the best experts on this subject based on the ideXlab platform.
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osteocyte and late osteoblast derived Notum reduces cortical bone mass in mice
American Journal of Physiology-endocrinology and Metabolism, 2021Co-Authors: Karin H Nilsson, Christine Perret, Petra Henning, Antti Koskela, Juha Tuukkanen, Maha El Shahawy, Ulf H Lerner, Claes Ohlsson, Sofia MoverareskrticAbstract:Osteoporosis is a common skeletal disease, with increased risk of fractures. Currently available osteoporosis treatments reduce the risk of vertebral fractures, mainly dependent on trabecular bone, whereas the effect on nonvertebral fractures, mainly dependent on cortical bone, is less pronounced. WNT signaling is a crucial regulator of bone homeostasis, and the activity of WNTs is inhibited by Notum, a secreted WNT lipase. We previously demonstrated that conditional inactivation of Notum in all osteoblast lineage cells increases the cortical but not the trabecular bone mass. The aim of the present study was to determine if Notum increasing cortical bone is derived from osteoblast precursors/early osteoblasts or from osteocytes/late osteoblasts. First, we demonstrated Notum mRNA expression in Dmp1-expressing osteocytes and late osteoblasts in cortical bone using in situ hybridization. We then developed a mouse model with inactivation of Notum in Dmp1-expressing osteocytes and late osteoblasts (Dmp1-creNotumflox/flox mice). We observed that the Dmp1-creNotumflox/flox mice displayed a substantial reduction of Notum mRNA in cortical bone, resulting in increased cortical bone mass and decreased cortical porosity in femur but no change in trabecular bone volume fraction in femur or in the lumbar vertebrae L5 in Dmp1-creNotumflox/flox mice as compared with control mice. In conclusion, osteocytes and late osteoblasts are the principal source of Notum in cortical bone, and Notum derived from osteocytes/late osteoblasts reduces cortical bone mass. These findings demonstrate that inhibition of osteocyte/late osteoblast-derived Notum might be an interesting pharmacological target to increase cortical bone mass and reduce nonvertebral fracture risk.NEW & NOTEWORTHY Notum produced by osteoblasts is known to regulate cortical bone mass. Our new findings show that Notum specifically derived by DMP1-expressing osteocytes and late osteoblasts regulates cortical bone mass and not trabecular bone mass.
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osteoblast derived Notum reduces cortical bone mass in mice and the Notum locus is associated with bone mineral density in humans
The FASEB Journal, 2019Co-Authors: Sofia Moverareskrtic, Karin Nilsson, Petra Henning, Thomas Funckbrentano, Maria Nethander, Fernando Rivadeneira, Glaucia Coletto Nunes, Antti Koskela, Juha Tuukkanen, Jan TuckermannAbstract:Osteoporosis is a common skeletal disease, affecting millions of individuals worldwide. Currently used osteoporosis treatments substantially reduce vertebral fracture risk, whereas nonvertebral fracture risk, mainly caused by reduced cortical bone mass, has only moderately been improved by the osteoporosis drugs used, defining an unmet medical need. Because several wingless-type MMTV integration site family members (WNTs) and modulators of WNT activity are major regulators of bone mass, we hypothesized that Notum, a secreted WNT lipase, might modulate bone mass via an inhibition of WNT activity. To characterize the possible role of endogenous Notum as a physiologic modulator of bone mass, we developed global, cell-specific, and inducible Notum-inactivated mouse models. Notum expression was high in the cortical bone in mice, and conditional Notum inactivation revealed that osteoblast lineage cells are the principal source of Notum in the cortical bone. Osteoblast lineage-specific Notum inactivation increased cortical bone thickness via an increased periosteal circumference. Inducible Notum inactivation in adult mice increased cortical bone thickness as a result of increased periosteal bone formation, and silencing of Notum expression in cultured osteoblasts enhanced osteoblast differentiation. Large-scale human genetic analyses identified genetic variants mapping to the Notum locus that are strongly associated with bone mineral density (BMD) as estimated with quantitative ultrasound in the heel. Thus, osteoblast-derived Notum is an essential local physiologic regulator of cortical bone mass via effects on periosteal bone formation in adult mice, and genetic variants in the Notum locus are associated with BMD variation in adult humans. Therapies targeting osteoblast-derived Notum may prevent nonvertebral fractures.-Moverare-Skrtic, S., Nilsson, K. H., Henning, P., Funck-Brentano, T., Nethander, M., Rivadeneira, F., Coletto Nunes, G., Koskela, A., Tuukkanen, J., Tuckermann, J., Perret, C., Souza, P. P. C., Lerner, U. H., Ohlsson, C. Osteoblast-derived Notum reduces cortical bone mass in mice and the Notum locus is associated with bone mineral density in humans.
Myriam Zecca - One of the best experts on this subject based on the ideXlab platform.
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subdivision of the drosophila wing imaginal disc by egfr mediated signaling
Development, 2002Co-Authors: Myriam Zecca, Gary StruhlAbstract:Growth and patterning of the Drosophila wing imaginal disc depends on its subdivision into dorsoventral (DV) compartments and limb (wing) and body wall (Notum) primordia. We present evidence that both the DV and wing-Notum subdivisions are specified by activation of the Drosophila Epidermal Growth Factor Receptor (EGFR). We show that EGFR signaling is necessary and sufficient to activate apterous (ap) expression, thereby segregating the wing disc into D (ap-ON) and V (ap-OFF) compartments. Similarly, we demonstrate that EGFR signaling directs the expression of Iroquois Complex (Iro-C) genes in prospective Notum cells, rendering them distinct from, and immiscible with, neighboring wing cells. However, EGFR signaling acts only early in development to heritably activate ap, whereas it is required persistently during subsequent development to maintain Iro-C gene expression. Hence, as the disc grows, the DV compartment boundary can shift ventrally, beyond the range of the instructive EGFR signal(s), in contrast to the Notum-wing boundary, which continues to be defined by EGFR input.
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control of growth and patterning of the drosophila wing imaginal disc by egfr mediated signaling
Development, 2002Co-Authors: Myriam Zecca, Gary StruhlAbstract:The subdivision of the Drosophila wing imaginal disc into dorsoventral (DV) compartments and limb-body wall (wing-Notum) primordia depends on Epidermal Growth Factor Receptor (EGFR) signaling, which heritably activates apterous (ap) in D compartment cells and maintains Iroquois Complex (Iro-C) gene expression in prospective Notum cells. We examine the source, identity and mode of action of the EGFR ligand(s) that specify these subdivisions. Of the three known ligands for the Drosophila EGFR, only Vein (Vn), but not Spitz or Gurken, is required for wing disc development. We show that Vn activity is required specifically in the dorsoproximal region of the wing disc for ap and Iro-C gene expression. However, ectopic expression of Vn in other locations does not reorganize ap or Iro-C gene expression. Hence, Vn appears to play a permissive rather than an instructive role in organizing the DV and wing-Notum segregations, implying the existance of other localized factors that control where Vn-EGFR signaling is effective. After ap is heritably activated, the level of EGFR activity declines in D compartment cells as they proliferate and move ventrally, away from the source of the instructive ligand. We present evidence that this reduction is necessary for D and V compartment cells to interact along the compartment boundary to induce signals, like Wingless (Wg), which organize the subsequent growth and differentiation of the wing primordium.
