El Castillo de Bejís: noticia de los trabajos arqueológicos efectuados y hallazgo de un fragmento de inscripción romana

La actuación que hemos llevado a cabo en el Castillo de Bejís se enmarca dentro del 'Proyecto básico y de ejecución de consolidaciones urgentes de fábricas del Castillo de Bejís'. El planteamiento inicial era la realización de una serie de sondeos arqueológicos en la zona de la muralla noroeste. Sin embargo, las intervenciones contempladas en el proyecto arquitectónico suponían remoción de tierras, por lo que los trabajos arqueológicos en el Castillo contemplaron además de la apertura de cuatro sondeos el seguimiento de todas las actividades dentro del recinto fortificado que supusieran movimientos de tierra

Un sondeig en la via Augusta entre els termes municipals de la Pobla Tornesa i Vilafamés (la Plana Alta, Castelló)

En este artículo se explican los resultados del sondeo realizado en la vía Augusta entre los términos municipales de La Pobla Tornesa y Vilafamés (Castellón). Se han podido obtener datos sobre la técnica constructiva utilizada, su anchura y su estado de conservación

Troballa de nivells iberoromans en una excavació urbana a Peníscola (el Baix Maestrat).

En este artículo damos a conocer los resultados de una excavación realizada en la población de Peñíscola, situada al norte de la costa valenciana. En ella se han documentado por primera vez niveles arqueológicos que pueden fecharse en el siglo II aC. Este modesto hallazgo confirma la hipótesis de que el tómbolo que ocupa la localidad fue ocupado en la antigüedad. In this paper we present the results of an excavation in the town of Peñíscola, situated north of the Valencian coast. It has been documented for the first time archaeological levels datable in the second century BC. This modest finding confirms the hypothesis that the tombolo where the town sits was occupied in antiquity

The hormonal pathway controlling cell death during metamorphosis in a hemimetabolous insect

AbstractMetamorphosis in holometabolous insects is mainly based on the destruction of larval tissues. Intensive research in Drosophila melanogaster, a model of holometabolan metamorphosis, has shown that the steroid hormone 20-hydroxyecdysone (20E) signals cell death of larval tissues during metamorphosis. However, D. melanogaster shows a highly derived type of development and the mechanisms regulating apoptosis may not be representative in the insect class context. Unfortunately, no functional studies have been carried out to address whether the mechanisms controlling cell death are present in more basal hemimetabolous species. To address this, we have analyzed the apoptosis of the prothoracic gland of the cockroach Blattella germanica, which undergoes stage-specific degeneration just after the imaginal molt. Here, we first show that B. germanica has two inhibitor of apoptosis (IAP) proteins and that one of them, BgIAP1, is continuously required to ensure tissue viability, including that of the prothoracic gland, during nymphal development. Moreover, we demonstrate that the degeneration of the prothoracic gland is controlled by a complex 20E-triggered hierarchy of nuclear receptors converging in the strong activation of the death-inducer Fushi tarazu-factor 1 (BgFTZ-F1) during the nymphal–adult transition. Finally, we have also shown that prothoracic gland degeneration is effectively prevented by the presence of juvenile hormone (JH). Given the relevance of cell death in the metamorphic process, the characterization of the molecular mechanisms regulating apoptosis in hemimetabolous insects would allow to help elucidate how metamorphosis has evolved from less to more derived insect species

The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species

31 p.-11 fig.-2 tab.+ Erratum (2 p.) Papanikolaou, Alexie et al.Background: The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control.Results: The 479 Mb medfly genome is sequenced from adult flies from lines inbred for 20 generations. A highquality assembly is achieved having a contig N50 of 45.7 kb and scaffold N50 of 4.06 Mb. In-depth curation of more than 1800 messenger RNAs shows specific gene expansions that can be related to invasiveness and host adaptation, including gene families for chemoreception, toxin and insecticide metabolism, cuticle proteins, opsins, and aquaporins. We identify genes relevant to IPM control, including those required to improve SIT.Conclusions: The medfly genome sequence provides critical insights into the biology of one of the most serious and widespread agricultural pests. This knowledge should significantly advance the means of controlling the size and invasive potential of medfly populations. Its close relationship to Drosophila, and other insect species important to agriculture and human health, will further comparative functional and structural studies of insect genomes that should broaden our understanding of gene family evolutionSupport of this project was provided by the U.S. Department of Agriculture(USDA), Agricultural Research Service (ARS), Animal and Plant Health Inspection Service (APHIS), and National Institute of Food and Agriculture(NIFA)-Biotechnology Risk Assessment Grants Program (grant #2011-39211-30769 to AMH) for funding the initial phase of this project, and to the National Institutes of Health (NIH)-National Human Genome Research Institute (NHGRI) for funding the medfly genome sequencing, assembly and Maker 2.0 automated annotation as part of the i5K 30 genome pilot project (grant #U54 HG003273 to RAG). The NIH Intramural Research Program, National Library of Medicine funded the NCBI Gnomon annotation and the USDA-National Agricultural Library (NAL) provided support for the WebApollo curation website, with support for manual curation training (to MM-T) provided by NIGMS (grant #5R01GM080203),NHGRI (grant #5R01HG004483), and the U.S. Department of Energy(contract #DE-AC02-05CH11231). Support was provided for: toxin metabolism and insecticide resistance gene studies from MINECO,Spain (AGL2013-42632-R to FO and PH-C); microRNAs, horizontal gene transfer and bacterial contaminant studies from the European Social Fund and National Strategic Reference Framework-THALES (MIS375869 to KB, GT, AGH, and KM) and the U.S. National Science Foundation(DEB 1257053 to JHW); cuticle protein gene studies from USDA-NIFA(grant #2016-67012-24652 to AJR); sex-determination studies from L.R. Campania (grant 5/02, 2008 to GS); male reproduction and sexual differentiation studies from the FAO/IAEA (Technical Contract No: 16966 to GGa) and Cariplo IMPROVE (to FS); and programmed cell death gene studies and genomic data analysis (to MFS) from the Emmy Noether program, DFG(SCHE 1833/1-1) and the LOEWE Center for Insect Biotechnology & Bioresources grant of the Hessen State Ministry of Higher Education, Research and the Arts(HMWK), Germany and from the USDA-NIFA-Biotechnology Risk Assessment Grants Program (grant #2015-33522-24094 to AMH).Peer reviewe

Functional characterization and fitness cost of spinosad-resistant alleles in Ceratitis capitata

[EN] The sustainability of control programs for the Mediterranean fruit fly, Ceratitis capitata, for citrus crops in Spain has been threatened by the development of resistance to malathion and lambda-cyhalothrin in recent years. Spinosad is widely used without apparent loss of efficacy. However, a highly resistant strain, JW-100s, has been obtained after laboratory selection. Spinosad resistance in JW-100s has been associated with different mutant alleles of the alpha 6 subunit of the nicotinic acetylcholine receptor (Cc alpha 6) including an isoform-specific truncation allele, Cc alpha 6(3aQ68*). Using the GAL4 > UAS system in Drosophila melanogaster to demonstrate expression of this truncated alpha 6 subunit, in a d alpha 6 loss-of-function genetic background, does not rescue susceptibility to spinosad, while the expression of Cc alpha 6 wild-type isoforms does. We have also generated C. capitata isolines from JW-100s homozygous for: (1) the Cc alpha 6(3aQ68*Delta 3b-4) allele, which contains the mutation 3aQ68*, and (2) the Cc alpha 6(3aQ68*-K352*) allele, which contains the mutations 3aQ68* and K352*. Neither of these produce complete Cc alpha 6 transcripts. The frequency of resistant alleles declined when in competition with individuals carrying the wild-type allele. Through extensive testing of both biological and behavioral fitness traits, we identified a reduced ability of Cc alpha 6(3aQ68*Delta 3b-4) males to detect the parapheromone and to mate with females carrying the Cc alpha 6(3aQ68*-K352*) allele in competition experiments. Thus, not only the potential for spontaneous resistant mutations to arise in Cc alpha 6 but also their fitness costs must be considered when planning resistance management strategies for C. capitata.This work received financial support from CICYT (AGL2016-76516-R). The Spanish MINECO granted A. Guillem-Amat a predoc (BES-C-2014-068937) and a mobility (EEBB-I-16-11336) fellowships. We gratefully acknowledge Maria Torne (Dow Agro-Science Iberica) for providing technical grade spinosad, Charles Robin (University of Melbourne) for assisting with bureaucratic issues with the Australian Government, Tinna Yang (University of Melbourne) for the keeping and shipping of the flies and Sandra Vacas (Universitat Politecnica de Valencia) for the scientific advice on electroantennography.Guillem-Amat, A.; Ureña, E.; López-Errasquín, E.; Navarro-Llopis, V.; Batterham, P.; Sánchez, L.; Perry, T.... (2020). Functional characterization and fitness cost of spinosad-resistant alleles in Ceratitis capitata. Journal of Pest Science. 93(3):1043-1058. https://doi.org/10.1007/s10340-020-01205-xS10431058933Abbas N, Mansoor MM, Shad SA et al (2014) Fitness cost and realized heritability of resistance to spinosad in Chrysoperla carnea (Neuroptera: Chrysopidae). 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BMC Evol Biol 7:1–12. https://doi.org/10.1186/1471-2148-7-98Jones AK, Raymond-Delpech V, Thany SH et al (2006) The nicotinic acetylcholine receptor gene family of the honey bee, Apis mellifera. Genome Res 16:1422–1430. https://doi.org/10.1101/gr.4549206Khan HAA, Akram W, Shad SA (2014) Genetics, cross-resistance and mechanism of resistance to spinosad in a field strain of Musca domestica L. (Diptera: Muscidae). Acta Trop 130:148–154. https://doi.org/10.1016/j.actatropica.2013.11.006Li ZM, Liu SS, Liu YQ, Ye GY (2007) Temperature-related fitness costs of resistance to spinosad in the diamondback moth, Plutella xylostella (Lepidoptera: Plutelidae). Bull Entomol Res 97:627–635. https://doi.org/10.1017/S0007485307005366Li X, Wan Y, Yuan G et al (2017) Fitness trade-off associated with spinosad resistance in Frankliniella occidentalis (Thysanoptera: Thripidae). J Econ Entomol 110:1755–1763. https://doi.org/10.1093/jee/tox122Magaña C, Hernandez-Crespo P, Ortego F, Castañera P (2007) Resistance to malathion in field populations of Ceratitis capitata. J Econ Entomol 100:1836–1843. https://doi.org/10.1603/0022-0493(2007)100%5b1836:rtmifp%5d2.0.co;2Magaña C, Hernández-Crespo P, Brun-Barale A et al (2008) Mechanisms of resistance to malathion in the medfly Ceratitis capitata. Insect Biochem Mol Biol 38:756–762. https://doi.org/10.1016/j.ibmb.2008.05.001MAPA (2019) Ministerio de Agricultura, Pesca y Alimentación. https://www.mapa.gob.es/es/. Accessed 12 Jun 2019Navarro-Llopis V, Primo J, Vacas S (2015) Bait station devices can improve mass trapping performance for the control of the Mediterranean fruit fly. Pest Manag Sci 71:923–927. https://doi.org/10.1002/ps.3864Okuma DM, Bernardi D, Horikoshi RJ et al (2018) Inheritance and fitness costs of Spodoptera frugiperda (Lepidoptera: Noctuidae) resistance to spinosad in Brazil. Pest Manag Sci 74:1441–1448. https://doi.org/10.1002/ps.4829Perry T, Batterham P (2018) Harnessing model organisms to study insecticide resistance. Curr Opin Insect Sci 27:61–67. https://doi.org/10.1016/j.cois.2018.03.005Perry T, McKenzie JA, Batterham P (2007) A D α6 knockout strain of Drosophila melanogaster confers a high level of resistance to spinosad. Insect Biochem Mol Biol 37:184–188. https://doi.org/10.1016/j.ibmb.2006.11.009Perry T, Batterham P, Daborn PJ (2011) The biology of insecticidal activity and resistance. Insect Biochem Mol Biol 41:411–422. https://doi.org/10.1016/j.ibmb.2011.03.003Perry T, Somers J, Yang YT, Batterham P (2015) Expression of insect α6-like nicotinic acetylcholine receptors in Drosophila melanogaster highlights a high level of conservation of the receptor: spinosyn interaction. Insect Biochem Mol Biol 64:106–115. https://doi.org/10.1016/j.ibmb.2015.01.017Puinean AM, Lansdell SJ, Collins T et al (2013) A nicotinic acetylcholine receptor transmembrane point mutation (G275E) associated with resistance to spinosad in Frankliniella occidentalis. J Neurochem 124:590–601. https://doi.org/10.1111/jnc.12029Raymond M, Berticat C, Weill M et al (2001) Insecticide resistance in the mosquito Culex pipiens: what have we learned about adaptation? Genetica 112–113:287–296. https://doi.org/10.1023/A:1013300108134Reddy PVR, Rashmi MA (2016) Sterile insect technique (SIT) as a component of area-wide integrated management of fruit flies: status and scope. Pest Manag Hortic Ecosyst 22:1–11. https://doi.org/10.1097/01.ede.0000100289.82156.8bRehan A, Freed S (2014) Selection, mechanism, cross resistance and stability of spinosad resistance in Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae). Crop Prot 56:10–15. https://doi.org/10.1016/j.cropro.2013.10.013Rehan A, Freed S (2015) Fitness cost of methoxyfenozide and the effects of its sublethal doses on development, reproduction, and survival of spodoptera litura (Fabricius) (Lepidoptera: Noctuidae). Neotrop Entomol 44:513–520. https://doi.org/10.1007/s13744-015-0306-5Rinkevich FD, Scott JG (2009) Transcriptional diversity and allelic variation in nicotinic acetylcholine receptor subunits of the red flour beetle, Tribolium castaneum. Insect Mol Biol 18:233–242. https://doi.org/10.1111/j.1365-2583.2009.00873.xRinkevich FD, Chen M, Shelton AM, Scott JG (2010) Transcripts of the nicotinic acetylcholine receptor subunit gene Pxyla6 with premature stop codons are associated with spinosad resistance in diamondback moth, Plutella xylostella. Invertebr Neurosci 10:25–33. https://doi.org/10.1007/s10158-010-0102-1Robertson JL, Preisler HK (1992) Pesticide bioassays with arthropods. 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Trametinib ameliorates aging-associated gut pathology in Drosophila females by reducing Pol III activity in intestinal stem cells

Pharmacological therapies are promising interventions to slow down aging and reduce multimorbidity in the elderly. Studies in animal models are the first step toward translation of candidate molecules into human therapies, as they aim to elucidate the molecular pathways, cellular mechanisms, and tissue pathologies involved in the anti-aging effects. Trametinib, an allosteric inhibitor of MEK within the Ras/MAPK (Ras/Mitogen-Activated Protein Kinase) pathway and currently used as an anti-cancer treatment, emerged as a geroprotector candidate because it extended lifespan in the fruit fly Drosophila melanogaster. Here, we confirm that trametinib consistently and robustly extends female lifespan, and reduces intestinal stem cell (ISC) proliferation, tumor formation, tissue dysplasia, and barrier disruption in guts in aged flies. In contrast, pro-longevity effects of trametinib are weak and inconsistent in males, and it does not influence gut homeostasis. Inhibition of the Ras/MAPK pathway specifically in ISCs is sufficient to partially recapitulate the effects of trametinib. Moreover, in ISCs, trametinib decreases the activity of the RNA polymerase III (Pol III), a conserved enzyme synthesizing transfer RNAs and other short, non-coding RNAs, and whose inhibition also extends lifespan and reduces gut pathology. Finally, we show that the pro-longevity effect of trametinib in ISCs is partially mediated by Maf1, a repressor of Pol III, suggesting a life-limiting Ras/MAPK-Maf1-Pol III axis in these cells. The mechanism of action described in this work paves the way for further studies on the anti-aging effects of trametinib in mammals and shows its potential for clinical application in humans

Autophagic dysfunction and gut microbiota dysbiosis cause chronic immune activation in a Drosophila model of Gaucher disease

Mutations in the GBA1 gene cause the lysosomal storage disorder Gaucher disease (GD) and are the greatest known genetic risk factors for Parkinson’s disease (PD). Communication between the gut and brain and immune dysregulation are increasingly being implicated in neurodegenerative disorders such as PD. Here, we show that flies lacking the Gba1b gene, the main fly orthologue of GBA1, display widespread NF-kB signalling activation, including gut inflammation, and brain glial activation. We also demonstrate intestinal autophagic defects, gut dysfunction, and microbiome dysbiosis. Remarkably, modulating the microbiome of Gba1b knockout flies, by raising them under germ-free conditions, partially ameliorates lifespan, locomotor and immune phenotypes. Moreover, we show that modulation of the immune deficiency (IMD) pathway is detrimental to the survival of Gba1 deficient flies. We also reveal that direct stimulation of autophagy by rapamycin treatment achieves similar benefits to germ-free conditions independent of gut bacterial load. Consistent with this, we show that pharmacologically blocking autophagosomal-lysosomal fusion, mimicking the autophagy defects of Gba1 depleted cells, is sufficient to stimulate intestinal immune activation. Overall, our data elucidate a mechanism whereby an altered microbiome, coupled with defects in autophagy, drive chronic activation of NF-kB signaling in a Gba1 loss-of-function model. It also highlights that elimination of the microbiota or stimulation of autophagy to remove immune mediators, rather than prolonged immunosuppression, may represent effective therapeutic avenues for GBA1-associated disorders

The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species

The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control

Regulació de la metamorfosi en insectes hemimetàbols i holometàbols. Caracterització funcional del Gen E93 i del procés de sumoilació

Treball realitzat a la Unitat de Genòmica Funcional i Evolució de l’Institut de Biologia Evolutiva (IBE, CSIC‐UPF).-- Universitat de Barcelona, Facultat de Biologia, Departament de Fisiologia, programa de Fisiologia.-- Tutora de la tesis: Encarnación Capilla Campos.-- Esta tesis doctoral está sujeta a la licencia Reconocimiento - NoComercial – SinObraDerivada 3.0. España de Creative Commons.[CAT] La maduració sexual dels animals està controlada per hormones. En els insectes alats aquesta maduració es coneix amb el nom de metamorfosi, i pot anar acompanyada d’una completa reorganització de la majoria d’òrgans i estructures juvenils (insectes holometàbols), o bé limitar-se a uns pocs teixits, principalment les ales i la genitàlia (insectes hemimetàbols). La metamorfosi dels insectes holometàbols (metamorfosi completa), que va aparèixer fa uns 300 milions d’anys a partir d’insectes hemimetàbols (metamorfosi incompleta), ha fet que aquest grup animal assolís un gran èxit evolutiu, ja que la diferent morfologia entre les formes juvenils i adultes els permet explotar hàbitats diferents i no competir entre elles. En tots els insectes els canvis metamòrfics estan controlats per dues hormones, la 20-hidroxiecdisona (20E) i l’hormona juvenil (HJ). La 20E s’encarrega d’induir les transicions entre les diverses mudes i estadis del desenvolupament, mentre que l’HJ modula la naturalesa d’aquestes transicions. La present tesi doctoral pretén aprofundir en el coneixement de la regulació molecular de la metamorfosi mitjançant l’estudi del procés de sumoilació, per una banda, i de la funció del gen E93 de l’altra. Per fer-ho s’han utilitzat tres models d’insectes: la panerola Blattella germanica (hemimetàbol), l’escarabat Tribolium castaneum (holometàbol basal) i la mosca Drosophila melanogaster (holometàbol modificat). La sumoilació és una modificació posttraduccional que consisteix en la unió de manera reversible d’una proteïna petita, anomenada Sumo (de l’anglès Small Ubiquitin-like MOdifier), a una proteïna diana. Aquesta unió comporta la modificació de les propietats de la proteïna diana canviant-ne la conformació, la localització subcel•lular, la capacitat d’interacció amb altres proteïnes o la capacitat d’unió al DNA (en el cas dels factors de transcripció), entre d’altres. En els insectes, l’estudi del procés de sumoilació s’havia centrat fins ara en l’holometàbol D. melanogaster, on s’ha vist que és imprescindible per a l’inici de la metamorfosi. En aquesta tesi doctoral s’ha descrit la funció d’aquest procés en el desenvolupament postembrionari d’un insecte molt més basal, B. germanica. Aquesta panerola té dos paràlegs Sumo, BgSumo1 i BgSumo3, mentre que D. melanogaster en té tan sols un, Smt3. Aquest fet permetia, doncs, estudiar l’evolució funcional de la sumoilació en els insectes, i com aquesta funció està distribuïda en animals amb dos proteïnes Sumo. Així, mitjançant la tècnica de l’RNA d’interferència in vivo, s’ha comprovat que la sumoilació és essencial per a la supervivència durant el desenvolupament postembrionari de B. germanica.A més, s’ha vist que el paràleg BgSumo1 és necessari per a que es doni correctament la muda imaginal, per a la transducció del senyal de la 20E durant aquesta muda i per a la proliferació de l’epiteli fol•licular de l’oòcit basal. D’altra banda, s’ha comprovat que diversos receptors nuclears que conformen la via de senyalització de la 20E, imprescindible per a l’inici de la metamorfosi, són capaços de sumoilar-se en condicions in vitro. La segona part del treball se centra en l’estudi funcional del factor de transcripció E93. Aquest, descrit prèviament en D. melanogaster com el responsable de la transmissió del senyal de la 20E en el procés de mort cel•lular programada durant la metamorfosi, s’ha comprovat en aquesta tesi que actua de regulador molt més general dels processos metamòrfics. Així, s’expressa fortament durant el període metamòrfic en els tres models estudiats (B. germanica, T. castaneum i D. melanogaster), i la seva absència bloqueja aquest procés. En l’hemimetàbol B. germanica, la manca de BgE93 durant el darrer estadi nimfal provoca la formació de nimfes supernumeràries, que mai assoleixen l’estadi adult. En l’holometàbol basal T. castaneum, per altra banda, l’absència de TcE93 impedeix la diferenciació adulta que es dóna durant la fase pupal i provoca la muda a un segon estadi pupal supernumerari. Finalment, en l’holometàbol modificat D. melanogaster també provoca un bloqueig general de la metamorfosi. A més, en aquests tres insectes E93 s’encarrega de reprimir l’expressió dels factors de transcripció Broad i Krüppel homolog-1, la presència dels quals impedeix la diferenciació adulta durant el darrer estadi juvenil dels insectes. Per tot això, aquest treball ha pogut descriure el factor de transcripció E93 com l’especificador adult dels insectes alats, pas essencial per avançar en el coneixement de la regulació de la metamorfosi i en l’estudi de l’aparició de la metamorfosi completa a partir d’insectes hemimetàbols.[EN] All immature animals undergo remarkable morphological and physiological changes to become mature adults. In winged insects, metamorphic changes are either limited to a few tissues (hemimetaboly) or involve a complete reorganization of most tissues and organs (holometaboly). In both cases, adult differentiation requires a temporally regulated balance between cell death, tissue growth and morphogenesis. Two hormones control this balance, the steroid 20-hydroxyecdysone (20E) and juvenile hormone (JH). The main goal of this thesis is to characterize the molecular mechanisms underlying the metamorphic process in insects through (i) the study of sumoylation and (ii) the functional characterization of the E93 transcription factor. To this aim, the hemimetabolous cockroach Blattella germanica, as well as the basal holometabolous beetle Tribolium castaneum and the highly modified holometabolous fly Drosophila melanogaster were used. Sumoylation is a post-translational modification that consists on the covalent binding of a small protein, called Sumo (Small Ubiquitin-like MOdifier), to a target protein. This modification is involved in the regulation of various cellular processes such as nuclear-cytosolic transport, transcriptional regulation and progression of cell cycle, among others. Notably, whereas D. melanogaster has only one Sumo protein (Smt3), B. germanica has two, BgSumo1 and BgSumo3. In this thesis, by using RNAi in vivo experiments we have shown that, whereas BgSumo3 is dispensable for the correct development of B. germanica, reduction of BgSumo1 levels resulted in severe defects during the metamorphic transition, including a marked developmental delay due to impaired activation of the ecdysone-triggered signaling cascade. Furthermore, we have shown that all the proteins belonging to the ecdysone-dependent transcriptional cascade of nuclear hormone receptors (BgEcR, BgRXR, BgE75, BgHR3 and BgFTZ-F1) are SUMOylated in vitro. The second part of the thesis is focused on the functional characterization of the E93 gene. First described as a dedicated regulator of cell death, we have demonstrated that this factor controls all the metamorphic transformations in insects. Thus, in the hemimetabolous B. germanica the absence of E93 during the last nymphal instar causes the formation of supernumerary nymphal instars. Moreover, in the holometabolous T. castaneum and D. melanogaster the depletion of E93 impairs adult differentiation during the pupal period and, in the beetle, also causes the formation of a supernumerary pupal stage. Furthermore, E93 controls the essential downregulation of the anti-metamorphic factors Broad and Krüppel homolog-1, two proteins whose presence blocks adult metamorphosis during the pupal stage. In conclusion, our data demonstrate that, despite the evolutionary distance and the differences in the developmental strategies to reach adulthood, E93 is the universal adult specifier in winged insects.Peer Reviewe