References of "Thiry, Marc"
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See detailLocalization of rDNA transcription sites within reptilian nucleoli
Bartholomé, Odile ULg; Franck, Claire; Thiry, Marc ULg

Poster (2015, January 27)

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See detailChange in the protofilamentnumber and β5-tubulin appearance in supporting cells during development of the hearing organ.
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas ULg et al

Poster (2015, January)

The supporting cells of the hearing organ are characterized by the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a ... [more ▼]

The supporting cells of the hearing organ are characterized by the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor mammalian tubulin, the β5-tubulin, recently reported as a biomarker of cell proliferation. It was shown that a β-tubulin isoform can specify the microtubule architecture, as seen with the expression of the Moth β2 tubulin in the Drosophila testes which imposes the 16-protofilament (16pf) structure on the corresponding subset of Drosophila microtubules. Moreover, supporting cell microtubules are formed by 15pf instead of the canonical 13, a unique fact among vertebrates. Such a protofilament configuration has been observed in C. elegans’ neurons which are responsible for the mechanosensory sense of touch. It was also shown that these 15pf microtubules were essential to the proper functioning of these neurons. To determine the role of this particular tubulin in the auditory organ and its possible involvement in the formation of the unusual 15pf microtubules of supporting cells, we studied the spatiotemporal localization of β5-tubulin during development in rats from embryonic day 18 until P25 (25th postnatal day). Then we examined the fine structure of microtubules at the transmission electron microscope level (TEM). Our results showed that β5-tubulin, contrary to other β-tubulins, had a unique distribution in the cochlea. This β-tubulin appeared at a postnatal stage, before the opening of the Corti’s tunnel and is restricted to supporting cells, especially in pillar and Deiters’ cells. Our TEM study further indicated that these cells were composed by 13pf microtubules at P2, but by 15pf microtubules at P25. In conclusion, the architecture and composition of microtubules present in the supporting cells change during development of the Corti organ. Further experiments are now required to determine if these changes are related to the appearance of β5-tubulin. [less ▲]

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See detailA dynamic unfolded protein response contributes to the control of cortical neurogenesis
LAGUESSE, Sophie ULg; Creppe, Catherine ULg; Nedialkova, Dany et al

in Developmental Cell (2015)

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See detailMicroRNA-124 Regulates Cell Specification in the Cochlea through Modulation of Sfrp4/5.
Huyghe, Aurelia; Van Den Ackerveken, Priscilla ULg; SACHELI, Rosalie ULg et al

in Cell Reports (2015), 13

The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the ... [more ▼]

The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the specification of these progenitors remain elusive. In the present study, by combining microarray analyses with conditional deletion of Dicer in the developing inner ear, we identified that miR-124 controls cell fate in the developing organ of Corti. By targeting secreted frizzled-related protein 4 (Sfrp4) and Sfrp5, two inhibitors of the Wnt pathway, we showed that miR-124 controls the β-catenin-dependent and also the PCP-related non-canonical Wnt pathways that contribute to HC differentiation and polarization in the organ of Corti. Thus, our work emphasizes the importance of miR-124 as an epigenetic safeguard that fine-tunes the expression of genes critical for cell patterning during cochlear differentiation. [less ▲]

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See detailExpanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome Dermatosparaxis.
Van Damme, Tim; Colige, Alain ULg; Syx, Delfien et al

in Genetics in Medicine : Official Journal of the American College of Medical Genetics (2015)

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See detailEndothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer.
Bovy, Nicolas ULg; Blomme, Benoît ULg; Freres, Pierre ULg et al

in Oncotarget (2015)

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for ... [more ▼]

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression. They are secreted into the extracellular medium in vesicles called exosomes, which allow communication between cells via the transfer of their cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we demonstrated that endothelial cells can transfer miRNA to tumor cells via exosomes. Using miRNA profiling, we identified miR-503, which exhibited downregulated levels in exosomes released from endothelial cells cultured under tumoral conditions. The modulation of miR-503 in breast cancer cells altered their proliferative and invasive capacities. We then identified two targets of miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in breast cancer patients after neoadjuvant chemotherapy, which could be partly due to increased miRNA secretion by endothelial cells. Taken together, our data are the first to reveal the involvement of the endothelium in the modulation of tumor development via the secretion of circulating miR-503 in response to chemotherapy treatment. [less ▲]

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See detailDetection of rRNA synthesis sites within reptilian nucleoli
Bartholomé, Odile ULg; Thiry, Marc ULg; Franck, Claire

Poster (2014, December 13)

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See detailCytoskeletal changes in supporting cells of the auditory organ during development in rodents: the appearance of 15-protofilament microtubules and β5-tubulin isoform.
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas et al

Poster (2014, December)

A feature of the supporting cells of the organ of Corti is the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor ... [more ▼]

A feature of the supporting cells of the organ of Corti is the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor mammalian tubulin, the β5-tubulin [1], recently reported to be a biomarker for cancer outcome [2] and cell proliferation [3]. It was shown that a β-tubulin isoform can specify the microtubule architecture, as seen with the expression of the Moth β2 tubulin in the Drosophila testes which imposes the 16-protofilament (16pf) structure on the corresponding subset of Drosophila microtubules, which normally contain 13pf [4]. Moreover, supporting cell microtubules are formed by 15pf instead of the canonical 13, a unique fact among vertebrates [5]. Such a protofilament configuration has been observed in C. elegans’ neurons which are responsible for the mechanosensory sense of touch [6]. It was also shown that these 15pf microtubules were essential to the proper functioning of these mechanosensory neurons [6]. To determine the role of this particular tubulin in the auditory organ and its possible involvement in the formation of the unusual 15pf microtubules of supporting cells, we studied the spatiotemporal localization of β5-tubulin during development in rats from embryonic day 18 until P25 (25th postnatal day). Then we examined the fine structure of microtubules at the transmission electron microscope level. Our results showed that β5-tubulin, contrary to other β-tubulins, had a unique distribution in the cochlea. This β-tubulin appeared at a postnatal stage, before the opening of the Corti’s tunnel and are restricted to supporting cells, especially in pillar and Deiters’ cells. Electron microscopy further indicated that pillar and Deiters cells were composed by 13pf microtubules at P2, but by 15pf microtubules at P25. In conclusion, the architecture of microtubules seems to evolve during the development of the organ of Corti. Furthermore, β5-tubulin has the same localization than this structure and could be an interesting target. [less ▲]

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See detailLa symétrie du vivant : des organismes aux molécules
Thiry, Marc ULg

in Bulletin de la Société Royale des Sciences de Liège (2014, October 28), 83

Les êtres vivants possèdent des caractéristiques communes de symétrie et de dissymétrie. Celles-ci ne concernent pas uniquement l’organisation externe des organismes vivants mais impliquent aussi tous ... [more ▼]

Les êtres vivants possèdent des caractéristiques communes de symétrie et de dissymétrie. Celles-ci ne concernent pas uniquement l’organisation externe des organismes vivants mais impliquent aussi tous leurs niveaux d’organisation jusqu’aux molécules qui les constituent. Le monde vivant se singularise du monde inanimé par l’homochiralité des molécules biologiques. [less ▲]

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See detailUnveiling the effects of berenil, a DNA-binding drug, on Trypanosoma cruzi: implications for kDNA ultrastructure and replication.
Zuma, Aline Araujo; Cavalcanti, Danielle Pereira; Zogovich, Marcelo et al

in Parasitology research (2014)

Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits a single mitochondrion with an enlarged portion termed kinetoplast. This unique structure harbors the mitochondrial DNA (kDNA ... [more ▼]

Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits a single mitochondrion with an enlarged portion termed kinetoplast. This unique structure harbors the mitochondrial DNA (kDNA), composed of interlocked molecules: minicircles and maxicircles. kDNA is a hallmark of kinetoplastids and for this reason constitutes a valuable target in chemotherapeutic and cell biology studies. In the present work, we analyzed the effects of berenil, a minor-groove-binding agent that acts preferentially at the kDNA, thereby affecting cell proliferation, ultrastructure, and mitochondrial activity of T. cruzi epimastigote form. Our results showed that berenil promoted a reduction on parasite growth when high concentrations were used; however, cell viability was not affected. This compound caused significant changes in kDNA arrangement, including the appearance of membrane profiles in the network and electron-lucent areas in the kinetoplast matrix, but nuclear ultrastructure was not modified. The use of the TdT technique, which specifically labels DNA, conjugated to atomic force microscopy analysis indicates that berenil prevents the minicircle decatenation of the network, thus impairing DNA replication and culminating in the appearance of dyskinetoplastic cells. Alterations in the kinetoplast network may be associated with kDNA lesions, as suggested by the quantitative PCR (qPCR) technique. Furthermore, parasites treated with berenil presented higher levels of reactive oxygen species and a slight decrease in the mitochondrial membrane potential and oxygen consumption. Taken together, our results reveal that this DNA-binding drug mainly affects kDNA topology and replication, reinforcing the idea that the kinetoplast represents a potential target for chemotherapy against trypanosomatids. [less ▲]

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See detailUnveil the Mechanism of Action of Berenil, a DNA Binding Drug, on Trypanosoma cruzi
Zuma, Aline Araujo; Cavalcanti, Danielle Pereira; Thiry, Marc ULg et al

Poster (2014, September)

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See detailβ 5 tubulin and 15-protofilament microtubules appeared in supporting cells of the Corti’s organ during development in rodents
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas et al

Conference (2014, August 31)

A feature of the organ of Corti’s supporting cells is the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor ... [more ▼]

A feature of the organ of Corti’s supporting cells is the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor mammalian tubulin, the β5-tubulin [1], recently related as a biomarker for cancer outcome [2] and cell proliferation [3]. It was shown that a β-tubulin isoform can specified the microtubule architecture, such as the expression of the Moth β2 in the Drosophila testes imposed the 16 protofilaments (16pf) structure on the corresponding subset of Drosophila microtubules, which normally contain 13pf [4]. Moreover, supporting cell microtubules are formed by 15pf instead of the canonical 13, a unique fact among vertebrates [5]. Such a protofilament configuration has been observed in C. elegans’ neurons which are responsible for the mechanosensory sense of touch [6]. It was also shown that these 15pf microtubules were essential to the proper functioning of these mechanosensory neurons [6]. To determine the role of this particular tubulin in the auditory organ and its possible involvement in the formation of the unusual 15pf microtubules of supporting cells, we studied the spatiotemporal localization of β5-tubulin during development in rats from embryonic day 18 until P25 (25th postnatal day). We also analyzed the localization of β5-tubulin mRNA expression in the Corti’s organ. Then we examined the fine structure of microtubules at the electron microscope level. For these experiments, we used an early postnatal stage and a late postnatal stage. Our results showed that β5-tubulin, contrary to other β-tubulins, had a unique distribution in the cochlea. This β-tubulin appeared at a postnatal stage, before the opening of the Corti’s tunnel and being restricted to supporting cells, especially in pillar and Deiters cells,. The same localization of β5-tubulin mRNA was observed by in Situ Hybridization. Electron microscopy indicated further that Pillar and Deiters cells were composed by 15-protofilament microtubules at the late postnatal stage (P25). In conclusion, all these data strongly suggest that there is a relationship between the presence of β5-tubulin and 15-protofilament microtubules in the supporting cells of the auditory organ. Further studies are now needed to elucidate their role. [less ▲]

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See detailThe Transcription Factor EGR1 Localizes to the Nucleolus and Is Linked to Suppression of Ribosomal Precursor Synthesis
Ponti, Donatella; Bellenchi, Gian Carlo; Puca, Rosa et al

in PLoS ONE (2014), 9(5),

EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the ... [more ▼]

EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism. [less ▲]

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See detailBiologie cellulaire. Exercices et méthodes
Thiry, Marc ULg; Racano, Sandra; Rigo, Pierre ULg

Book published by Dunod (2014)

Cet ouvrage propose aux étudiants des premières années d’études supérieures une méthode progressive et conviviale pour comprendre et appliquer les concepts fondamentaux de la biologie cellulaire. Des ... [more ▼]

Cet ouvrage propose aux étudiants des premières années d’études supérieures une méthode progressive et conviviale pour comprendre et appliquer les concepts fondamentaux de la biologie cellulaire. Des bonus web avec des exercices d'entrainement supplémentaires complètent l'ouvrage. Cet ouvrage propose aux étudiants des premières années d’études supérieures une méthode progressive et conviviale pour comprendre et appliquer les concepts fondamentaux de la biologie cellulaire. À la suite de rappels de cours, sous forme de fiches, chaque chapitre propose des exercices de difficulté croissante pour s’évaluer : QCM, questions Vrai/Faux et exercices de synthèse. Les corrigés détaillés mettent en évidence la méthodologie. Des bonus web avec des exercices d’entraînement supplémentaires complètent l’ouvrage. [less ▲]

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See detailDeletion of the ORF9p acidic cluster impairs the nuclear egress of Varicella-zoster virus capsids.
Riva, Laura ULg; Thiry, Marc ULg; Lebrun, Marielle ULg et al

in Journal of virology (2014)

The protein encoded by the ORF9 is essential for Varicella-zoster virus (VZV) replication. Previous studies documented its presence in the trans-Golgi network and its involvement in secondary envelopment ... [more ▼]

The protein encoded by the ORF9 is essential for Varicella-zoster virus (VZV) replication. Previous studies documented its presence in the trans-Golgi network and its involvement in secondary envelopment. In this work, we deleted the ORF9p acidic cluster, destroying its interaction with ORF47p and resulting in a nuclear accumulation of both proteins. This phenotype results to an accumulation of primary enveloped capsids in the perinuclear space, reflecting a capsid de-envelopment defect. [less ▲]

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See detailVaricella-zoster virus induces the formation of dynamic nuclear capsid aggregates.
Lebrun, Marielle ULg; Thelen, Nicolas ULg; Thiry, Marc ULg et al

in Virology (2014), 454-455

The first step of herpesviruses virion assembly occurs in the nucleus. However, the exact site where nucleocapsids are assembled, where the genome and the inner tegument are acquired, remains ... [more ▼]

The first step of herpesviruses virion assembly occurs in the nucleus. However, the exact site where nucleocapsids are assembled, where the genome and the inner tegument are acquired, remains controversial. We created a recombinant VZV expressing ORF23 (homologous to HSV-1 VP26) fused to the eGFP and dually fluorescent viruses with a tegument protein additionally fused to a red tag (ORF9, ORF21 and ORF22 corresponding to HSV-1 UL49, UL37 and UL36). We identified nuclear dense structures containing the major capsid protein, the scaffold protein and maturing protease, as well as ORF21 and ORF22. Correlative microscopy demonstrated that the structures correspond to capsid aggregates and time-lapse video imaging showed that they appear prior to the accumulation of cytoplasmic capsids, presumably undergoing the secondary egress, and are highly dynamic. Our observations suggest that these structures might represent a nuclear area important for capsid assembly and/or maturation before the budding at the inner nuclear membrane. [less ▲]

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See detailDifferentiation of Boettcher's cells during postnatal development of rat cochlea.
Cloes, Marie ULg; Renson, Thomas; Johnen, Nicolas et al

in Cell and tissue research (2013), 354(3), 707716

Contrary to the highly specialized epithelial cells of the mammalian auditory organ, little is known about the surrounding cells and, in particular, Boettcher's cells (BC). Our morphological studies show ... [more ▼]

Contrary to the highly specialized epithelial cells of the mammalian auditory organ, little is known about the surrounding cells and, in particular, Boettcher's cells (BC). Our morphological studies show that, in rats, these cells began their differentiation around postnatal day 8 (P8) reaching maturity around P20, when they are completely covered by Hensen's and Claudius' cells. Tight junctions were noted near the apex of BC, providing that they were in direct contact with the endolymphatic space, between approximately P8 and P16. We observed gap junctions between BC and adjacent cells before the end of the covering process suggesting the additional involvement of BC in potassium recycling into the endolymph. Adherens junctions were also seen between BC throughout their maturation. Importantly, we noticed cytoplasmic secretory granules and an accumulated material, probably a secretion, in the intercellular space, between P8 and P25. These results indicate that BC could basally take part in the secretion of the extracellular matrix of the basilar membrane. Finally, we show that the basolateral interdigitations of BC are longer and more tighlty grouped at maturity and harbour urea transporters as early as P18. Our observations thus support the view that BC perform several functions. [less ▲]

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See detailClass V β Tubulin during the development of the organ of Corti in rat
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas ULg et al

Poster (2013, September 13)

In eutherian mammals, the organ responsible for the transduction of sound waves into nerve impulses is called the organ of Corti. This structure located within the cochlea, a portion of the inner ear, is ... [more ▼]

In eutherian mammals, the organ responsible for the transduction of sound waves into nerve impulses is called the organ of Corti. This structure located within the cochlea, a portion of the inner ear, is composed by two types of cells: sensory hair cells and non-sensory supporting cells. All these cells are distributed according to a specific arrangement along the whole length of the cochlea. A feature of the organ of Corti’s supporting cell is the presence of an abundant cytoskeleton. This one is mainly composed of microtubules, structures make up by tubulin heterodimers. The heterodimers consist of one molecule of α tubulin and one molecule of β tubulin. β tubulin isotypes are highly conserved in evolution and differ by only a few amino acid residues, implying that the isotypes may have functional significance. Organ of Corti’s supporting cells are constituted by class V β-tubulin, a minor mammalian tubulin (Bhattacharya et al., 2008). Moreover, their microtubules are formed by 15 protofilaments instead of the canonical 13, a unique fact among vertebrates (Banerjee et al., 2008). Such a configuration of protofilaments has been observed in C. elegans’ neurons which are responsible for the mechanosensory sense of touch (Bounoutas et al., 2009). It was also shown that these 15 protofilaments microtubules were essential to the proper functioning of these mechanosensory neurons (Bounoutas et al., 2009). Here we present the spatiotemporal localization of class V β-tubulin during the development of the organ of Corti in rats from embryonic day 18 (E18) until P25 (25th postnatal day). For this purpose, we have used immunolabelings on cryosections of whole cochlea. Our preliminary results demonstrate that class V β-tubulin has a unique distribution in the cochlea, being restricted to supporting cells, especially in pillar cells. [less ▲]

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