Measuring Elite Quality

The aim of this paper is two-fold. Firstly, we present a methodology to measure the novel concept of elite quality (EQ), that is, country’s elites’ propensity– on aggregate – to create value, rather than rent seek. A four-level architecture allows for both an overall quantification of a country’s EQ, as well as an in-depth analysis of specific political economy dimensions, such as elite power. Secondly, the Elite Quality Index (EQx) is brought to life using data on 72 indicators for 32 countries. Our index negatively correlates with inequality measures, which suggests that more powerful elites less inclined to run value creation business models will exacerbate inequality. A variety of robustness tests suggest that the EQx scores and ranking are robust to ceteris paribus changes in key modelling assumptions. Thus, the EQx offers a reliable framework and new tool to analyze the political economy of countries

Polycomb Controls Gliogenesis by Regulating the Transient Expression of the Gcm/Glide Fate Determinant

The Gcm/Glide transcription factor is transiently expressed and required in the Drosophila nervous system. Threshold Gcm/Glide levels control the glial versus neuronal fate choice, and its perdurance triggers excessive gliogenesis, showing that its tight and dynamic regulation ensures the proper balance between neurons and glia. Here, we present a genetic screen for potential gcm/glide interactors and identify genes encoding chromatin factors of the Trithorax and of the Polycomb groups. These proteins maintain the heritable epigenetic state, among others, of HOX genes throughout development, but their regulatory role on transiently expressed genes remains elusive. Here we show that Polycomb negatively affects Gcm/Glide autoregulation, a positive feedback loop that allows timely accumulation of Gcm/Glide threshold levels. Such temporal fine-tuning of gene expression tightly controls gliogenesis. This work performed at the levels of individual cells reveals an undescribed mode of Polycomb action in the modulation of transiently expressed fate determinants and hence in the acquisition of specific cell identity in the nervous system. © 2012 Popkova et al.Fondation pour la Recherche Médicale and by Centre Européen de Recherche en Biologie et en Médecine; Association pour la Recherche sur le Cancer; Institut National de la Santé et de la Recherche Médicale; Centre National de la Recherche Scientifique; Université de Strasbourg; Hôpital de Strasbourg; Institut National du Cancer; the Agence Nationale de la Recherche; Alma Mater Studiorum; Università di Bologna; European Research Council (ERC-2008-AdG No 232947); Institut National de la Santé et de la Recherche Médicale; Centre National de la Recherche Scientifique; European Network of Excellence EpiGeneSys; Fundacion Mutua Madrileña (FMM-2006) and Ministerio de Ciencia y Tecnología (BFU-2008-5404)Peer Reviewe

Measuring Elite Quality

The aim of this paper is two-fold. Firstly, we present a methodology to measure the novel concept of elite quality (EQ), that is, country’s elites’ propensity– on aggregate – to create value, rather than rent seek. A four-level architecture allows for both an overall quantification of a country’s EQ, as well as an in-depth analysis of specific political economy dimensions, such as elite power. Secondly, the Elite Quality Index (EQx) is brought to life using data on 72 indicators for 32 countries. Our index negatively correlates with inequality measures, which suggests that more powerful elites less inclined to run value creation business models will exacerbate inequality. A variety of robustness tests suggest that the EQx scores and ranking are robust to ceteris paribus changes in key modelling assumptions. Thus, the EQx offers a reliable framework and new tool to analyze the political economy of countries

Transcriptional regulation of the Glutamate/GABA/Glutamine cycle in adult glia controls motor activity and seizures in Drosophila

International audienceThe fruitfly Drosophila melanogaster has been extensively used as a genetic model for the maintenance of nervous system's functions. Glial cells are of utmost importance in regulating the neuronal functions in the adult organism and in the progression of neurological pathologies. Through a microRNA-based screen in adult Drosophila glia, we uncovered the essential role of a major glia developmental determinant, repo, in the adult fly. Here, we report that Repo expression is continuously required in adult glia to transcriptionally regulate the highly conserved function of neurotransmitter recycling in both males and females. Transient loss of Repo dramatically shortens fly lifespan, triggers motor deficits, and increases the sensibility to seizures, partly due to the impairment of the glutamate/GABA/glutamine cycle. Our findings highlight the pivotal role of transcriptional regulation of genes involved in the glutamate/GABA/glutamine cycle in glia to control neurotransmitter levels in neurons and their behavioral output. The mechanism identified here in Drosophila exemplifies how adult functions can be modulated at the transcriptional level and suggest an active synchronized regulation of genes involved in the same pathway. The process of neurotransmitter recycling is of essential importance in human epileptic and psychiatric disorders and our findings may thus have important consequences for the understanding of the role that transcriptional regulation of neurotransmitter recycling in astrocytes has in human disease.SIGNIFICANCE STATEMENT Glial cells are an essential support to neurons in adult life and have been involved in a number of neurological disorders. What controls the maintenance and modulation of glial functions in adult life is not fully characterized. Through a miR overexpression screen in adult glia in Drosophila, we identify an essential role in adult glia of repo, which directs glial differentiation during embryonic development. Repo levels modulate, via transcriptional regulation, the ability of glial cells to support neurons in the glutamate/GABA/glutamine cycle. This leads to significant abnormalities in motor behavior as assessed through a novel automated paradigm. Our work points to the importance of transcriptional regulation in adult glia for neurotransmitter recycling, a key process in several human neurological disorders

The Drosophila fragile X mental retardation protein participates in the piRNA pathway.

International audienceABSTRACT RNA metabolism controls multiple biological processes, and a specific class of small RNAs, called piRNAs, act as genome guardians by silencing the expression of transposons and repetitive sequences in the gonads. Defects in the piRNA pathway affect genome integrity and fertility. The possible implications in physiopathological mechanisms of human diseases have made the piRNA pathway the object of intense investigation, and recent work suggests that there is a role for this pathway in somatic processes including synaptic plasticity. The RNA-binding fragile X mental retardation protein (FMRP, also known as FMR1) controls translation and its loss triggers the most frequent syndromic form of mental retardation as well as gonadal defects in humans. Here, we demonstrate for the first time that germline, as well as somatic expression, of Drosophila Fmr1 (denoted dFmr1), the Drosophila ortholog of FMRP, are necessary in a pathway mediated by piRNAs. Moreover, dFmr1 interacts genetically and biochemically with Aubergine, an Argonaute protein and a key player in this pathway. Our data provide novel perspectives for understanding the phenotypes observed in Fragile X patients and support the view that piRNAs might be at work in the nervous system

PcG genes control glia proliferation.

<p>(A–E) Quantitative analysis of glia at L3 vein position. Graphs comparing animals of different genotypes for the number of glia present on the L3 vein by 20 hr APF. The Y-axis indicates the percentage of wings showing a given number of glia; the X-axis, the number of glia expressing the Repo protein. Color-code is used to distinguish the compared genotypes: (A) wt vs. <i>gcm-Gal4/+</i>, (B) wt vs. <i>gcm-Gal4</i>, (C) <i>gcm-Gal/+</i> vs. <i>gcm-Gal4</i>, (D) <i>gcm-Gal4</i> vs. <i>gcm-Gal4</i>; <i>Pc/+</i>. (A) In wild type wings, the number oscillates between 5 and 7, whereas in <i>gcm-Gal4/+</i> wings it oscillates between 3 and 9 cells. (B,C) <i>gcm-Gal4</i> homozygous animals carry fewer Repo labeled cells and less variation (from 3 to 6) than heterozygous animals (from 3 to 9). This is also reflected by the presence of one peak value for homozygous animals and two for heterozygous animals. (D) Note that <i>gcm-Gal4</i>; <i>Pc/+</i> animals show an increase of glial cell number compared to that observed in <i>gcm-Gal4</i> animals. (E) The graph shows the distribution around the average of the number of Repo+ cells in the different genotypes as indicated by the color code. (F–H) Quantitative analysis of glia at L1 vein position. Graphs comparing animals of different genotypes for the number of glia present on the L1 vein by 24 hr APF. The Y-axis indicates the percentage of wings showing a given number of glia; the X-axis, the quantitative range of Repo expressing cells. Color-code is used to distinguish the compared genotypes: (F) wt vs. <i>Pc/+</i> or vs. <i>E(z)/+</i>, (G) <i>Pc/+</i> vs. <i>E(z)/+</i> or vs. <i>Pc/E(z)</i>. (F) Most wild type animals show from 50 to 60 glia. (G) Note that most <i>Pc/E(z)</i> double heterozygous animals show higher number of glia (from 70 to 80 Repo+ cells) when compared to single heterozygous animals. This is confirmed by more than 20% of wings showing over one hundred Repo+ cells on L1 vein. (H) The graph shows the distribution around the average of the number of Repo+ glia at the L1 vein position in the different genotypes as indicated by the color-code. (I) Quantitative analysis of pupal wings showing a double Repo/PH3+ cell indicating glia proliferation.</p

The <i>Pc</i> mutation rescues the <i>gcm</i> LOF phenotype.

<p>(A,B) Schematic drawings showing the pupal wing at (A) 29 and (B) 16 hr APF (in all panels, anterior the top, distal to the right. Inset in (A) indicates the region shown in (C–F,I,N). L3-v, L3-1 and L3-3 indicate the sensory neurons. (C–R) Immunolabeling of 24 hr APF wings: <i>gcm-Gal4:UAS-GFP/+</i> (<i>gcm-Gal4/+</i>), considered as wt (C–H), <i>gcm-Gal4</i> (I–M) and <i>gcm-Gal4;Pc/+</i> (N–R). Anti-GFP labeling (green) reflects <i>gcm</i> expression, anti-Repo (red) marks glia and anti-Elav (blue) marks neurons. (C–H) Bracket in (E) indicates the glial cells produced by the L3-v sensory organ precursor; bracket in (F) indicates the three proximal neurons (L3-v, ACV, E1). White arrowhead indicates the L3-v neuron. Insets indicate the regions shown at higher magnification (C,I,N). (G,H) The L3-v GP produces several GFP+/Repo+ cells (arrows). In mutant wings (I–M), the L3-v lineage produces only one GFP+ cell (J,M), which does not express Repo (K), but Elav (L,M asterisk indicates the ectopic neuron). In double <i>gcm</i> and <i>Pc</i> LOF wings (N–R), several GFP+ cells (O,R) express Repo (P) and no ectopic neurons were observed (Q). (S) Quantitative data on the fate transformation phenotype at different stages. (T–V) Immunolabeling in 9 hr APF wings: <i>gcm-Gal4/+</i> (T–T″); <i>gcm-Gal4</i> (U–U″) and <i>gcm-Gal4;Pc/+</i> (V–V″). In all genotypes, one GFP+ cell produced by the L3-v lineage is visible (T,U,V). In the heterozygous wing, this cell expresses Repo (T′) and not Elav (T″). In <i>gcm-Gal4</i> (U), the GFP+ cell does not express Repo (U′), but expresses Elav (U″). In the double <i>gcm</i> and <i>Pc</i> LOF wing, the GFP+ cell (V, empty arrowhead) expresses Repo (V′) and Elav (V′). Scale bars: C–F,I,N = 100 µm; G,H,J–M,O–R,U–W″ = 10 µm.</p

Pc binds to the <i>gcm</i> promoter region.

<p>(A–B) Association of the <i>gcm</i> and <i>gcm2</i> loci with PcG proteins. (A) Levels of Polycomb (Pc) binding and H3K27me3 at the <i>gcm</i> or <i>gcm2</i> gene locus and control regions (GlacAT and Rp49) in <i>Drosophila</i> embryos were determined by quantitative ChIP (qChIP) experiments. Results are represented as percentage of input chromatin precipitated. The standard deviation was calculated from two independent experiments. (B) Organization of the <i>gcm-gcm2</i> loci, extent of the used transgenic constructs (blue lines) and ChIP-on-chip binding profiles of indicated PcG proteins and histone marks in <i>Drosophila</i> embryos. Data were extracted from <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003159#pgen.1003159-Schuettengruber4" target="_blank">[33]</a>. The plots show the ratios (fold change) of specific IP versus mock IP assays. Significantly enriched fragments (P-value<1×10⁻⁴) are shown in red. Black bars indicate the location of primers used for qChIP analysis. (C,D) Eyes from flies carrying an empty mini-<i>w⁺</i> transgenic vector (C) or a mini-<i>w⁺</i> vector including a 9 kb <i>gcm</i> transgene (D). Flies heterozygous for the transgene are on the left, homozygous ones on the right. (E–H) Polytene chromosome immuno-FISH experiments performed on the <i>gcm</i> locus and PcG proteins. Immuno-FISH staining in wt (<i>w¹¹¹⁸</i>) flies (E,F) or flies carrying a transgene including a 9 kb region upstream of the <i>gcm</i> TSS (G,H), with anti-Pc (E,G) or anti-Ph (F,H) antibodies. Nuclear DAPI labeling in blue. Right panels show higher magnifications of the inserts. Double labeling (E,F) with a <i>gcm</i> probe (E″,F″) and anti-Pc antibody (E′″) or anti-Ph antibodies (F′″) detects colocalization (arrow) at one Pc or Ph binding site in wt; transgenic animals (G–H) show a second site of colocalization. (G″–G′″, H-Hb′″). Colocalization of <i>gcm</i> and Ph (arrow) in wt (D) and in the transgenic line (F).</p

Genetic screen for <i>gcm^Pyx</i> modifiers and interactions with TrxG and PcG proteins.

<p>(A) Drawing of an adult notum. Small and large dots represent microchaetae and macrochaetae, respectively. Macrochaete symbols to the right. (B–E) Adult nota from wt (WT; B), <i>gcm^Pyx/+</i> (C), <i>gcm^Pyx</i>/suppressor deficiency (D), <i>gcm^Pyx</i>/enhancer deficiency (E) flies. Dfs = Deficiencies. Scale bar = 200 µm. Histograms present the average number of bristles per heminotum (y-axis) in different genotypes (x-axis). In all figures, average values are indicated +/− SEM (bars); <i>P-</i>values from t-test are indicated in the following way: *** (<i>P</i>≤10⁻³), ** (<i>P</i>≤10⁻²), * (P≤5×10⁻²). <i>Pyx</i> stands for <i>gcm^Pyx</i>. (F) Deficiencies deleting <i>brm</i>, (<i>Df(3L)brm11</i> and <i>Df(3L)th102</i>), as well as the <i>brm</i> mutation. <i>P-</i>values vs. <i>gcm^Pyx</i>/+: <i>gcm^Pyx</i>/+; <i>Df(3L)brm11/+</i> (8,9×10⁻⁶); <i>gcm^Pyx/+</i>; <i>Df(3L)th102/+</i> (0,02); <i>gcm^Pyx</i>/+; <i>brm/+</i> (4,2×10⁻⁷). (G) <i>gcm^Pyx</i> interaction with <i>trxG</i> genes. <i>P-</i>values vs. <i>gcm^Pyx</i>/+: <i>gcm^Pyx</i>/+; <i>brm/+</i> (4,2×10⁻⁷); <i>gcm^Pyx</i>/+; <i>osa/+</i> (0,002); <i>gcm^Pyx</i>/<i>UAS-osa; hsGal4/+</i> (0,0007); <i>gcm^Pyx</i>/+; <i>brm</i>/<i>osa</i> (3,4×10⁻⁸); <i>gcm^Pyx</i>/+; <i>trx/+</i> (0,009); <i>gcm^Pyx/+</i>; <i>ash1</i>/+ (0,01); <i>nej</i>/+; <i>gcm^Pyx/+</i> (6,9×10⁻⁷); <i>gcm^Pyx</i>/+; <i>E(bx)/+</i> (1,3×10⁻⁵). (H) <i>gcm^Pyx</i> interaction with <i>PcG</i> genes. Color code indicates members of the same complex (dark gray: PRC1, pale gray: PRC2, black: PRC recruiter). <i>P-</i>values vs. <i>gcm^Pyx</i>/+: <i>gcm^Pyx</i>/+; <i>Pc¹</i>/+ (6,2×10⁻⁶); <i>gcm^Pyx</i>/+; <i>Pc³</i>/+ (0,0022); <i>gcm^Pyx</i>/+; <i>Pc¹⁵</i>/+ (1,5×10⁻¹¹); <i>gcm^Pyx</i>/+; <i>E(z)</i>/+ (0,001); <i>gcm^Pyx</i>/<i>esc</i> (2,6×10⁻⁸); <i>gcm^Pyx</i>/<i>psq</i> (0,03). (I) Summary of the tested TrxG and PcG mutations. From left to right: the biochemical complex, the genes within the complex, the mutant phenotype over <i>gcm^Pyx</i> (No – no effect; S – suppressor; E – enhancer) and the large deficiency phenotype (nt – gene region not covered by the kit).</p