Дисертації з теми "Eph and ephrin interactions"
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Rodríguez, Franco Pilar. "Mechanics of boundary formation in epithelial monolayers by Eph-ephrin interactions." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/461913.
Повний текст джерелаPara que un organismo desarrolle y mantenga la homeostasis, a menudo los tipos celulares con distintas funciones deben estar separados por barreras físicas. La formación y mantenimiento de dichas barreras se suele atribuir a mecanismos locales restringidos a las células que las bordean. En este trabajo mostramos que, además de estos mecanismos subcelulares locales, la formación y el mantenimiento de las barreras físicas entre tejidos implica patrones mecánicos de largo alcance y larga duración. En particular, hemos analizado la formación de barreras epiteliales repulsivas entre dos monocapas epiteliales, una que expresa el receptor tirosina quinasa EphB2 y otra que expresa su ligando ephrinB1. Tras el contacto, ambas monocapas exhibieron patrones oscilatorios de fuerzas de tracción y tensiones intercelulares que involucraban varias hileras de células y que tendían a retirar las adhesiones célula-matriz hacia fuera de la barrera. Con el paso del tiempo, las monocapas se densificaron y los patrones mecánicos supracelulares se volvieron estables, contribuyendo así a mantener la segregación tisular permanentemente. La aglomeración de células fue acompañada por la aparición de ondas de deformación, similares a solitones, que se propagaron hasta más allá del campo de visión. Este fenómeno no es específico de las barreras repulsivas controladas por el par EphB2-ephrinB1, sino que también aparecen cuando una única monocapa interfiere con una interfaz inerte. Nuestros hallazgos revelan un mecanismo físico global que mantiene la separación entre tejidos independientemente de las características bioquímicas y mecánicas del límite tisular local.
Prévost, Nicolas. "Les interactions entre plaquettes assurent l'irreversibilité de l'agrégation plaquettaire : un rôle pour les récepteurs Eph et ephrines." Paris 7, 2004. http://www.theses.fr/2004PA077222.
Повний текст джерелаJungas, Thomas. "Caractérisation du rôle de la signalisation Eph-éphrine dans la division cellulaire." Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30102/document.
Повний текст джерелаCells within an organism successfully divide to ensure growth, differentiation and homeostasie. Recent work suggests that dividing cells actively communicate with neighbours thus spatially and temporally coordinating cell division while maintaining tissue cohesiveness. We hypothesized that Eph-ephrin signalling, a local cell-cell signalling pathway, could participate in coordinating cell division within a tissue. Using vertebrate and invertebrate cell culture models I showed that Eph-signalling controls cell division and induces delay in the abscission of nascent daughter cells as well as polyploidy. Using time-lapse imaging I proved that the Eph-mediated abscission failure depends on the catalytic activity of the receptor via the non receptor tyrosine kinase relay molecule c-Src. Downstream of Eph signalling c-Src phosphorylates the protein citron kinase (CitK) a well known regulator of intercellular bridge stability. I also observed that CitK was abnormally localized during cytokinesis when Eph signalling was active. Further, using in vitro kinase assays, I demonstrated that Eph does not directly phosphorylate CitK but that c-Src could do so. In addition, using Mass Spectrometry I mapped all tyrosine residues directly phosphorylated by c-Src. I mutated two of them located in the Rho binding domain of CitK and demonstrated that phosphorylation of those residues are necessary and sufficient to induce cytokinesis failure. I validated in vivo this novel role of Eph-ephrin signalling in a physiological context in the developing mouse neocortex. Members of the Eph/ephrin family are expressed in neural progenitors that give rise to neurons of the cortex upon neurogenic division. Importantly, CitK has been shown by others to control cytokinesis of these progenitor cells. Using the Cre-lox system, I specifically turned off Eph forward signalling in neural progenitor cells and observed an alteration of neuronal ploidy in these mutant animals. Further, I also observed that CitK which adopts a particular apical localisation in neural progenitors physiologically co-localized with phosphorylated tyrosine residues. Altogether, these results suggest that Eph-ephrin signalling controls abscission of neural progenitors by promoting phosphorylation of CitK. The textbook view of cytokinesis is that it is a cell autonomous event orchestrated by the intracellular machinery. Data obtained during my PhD suggest that cytokinesis is also regulated by local environment, here Eph/ephrin signalling, and that phosphorylation of CitK may represent a molecular switch in the normal progression of cell division and in the control of neuronal ploidy
Çelik, Arzu. "Restricted and complementary expression patterns of EPH receptors and Ephrin ligands define potential interaction sites in the embryonic and adult olfactory system of zebrafish, Danio rerio." [S.l. : s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964922754.
Повний текст джерелаZimmer, Manuel. "Mechanisms of Eph, ephrin mediated cell-cell communication." Diss., [S.l.] : [s.n.], 2003. http://edoc.ub.uni-muenchen.de/archive/00001547.
Повний текст джерелаGregory, L. G. L. "Eph-ephrin signalling in cell sorting and directional migration." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1318081/.
Повний текст джерелаBatson, Jennifer. "Regulation of contact inhibition of locomotion by Eph-ephrin signalling." Thesis, University of Bristol, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627947.
Повний текст джерелаFinkelmeier, Fabian [Verfasser]. "Die Rolle des Eph/Ephrin Systems bei Hirntumoren / Fabian Finkelmeier." Gießen : Universitätsbibliothek, 2011. http://d-nb.info/1063111358/34.
Повний текст джерелаFujii, Haruko. "Eph-ephrin A system regulates murine blastocyst attachment and spreading." Kyoto University, 2010. http://hdl.handle.net/2433/97940.
Повний текст джерелаCampbell, Jessica. "The regulation of cell migration and invasion by Eph-ephrin signalling." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.688221.
Повний текст джерелаMcCarron, Jennifer Kylie. "The role of the Eph and ephrin proteins in prostate cancer." Thesis, Queensland University of Technology, 2011. https://eprints.qut.edu.au/67918/1/Jennifer_McCarron_Thesis.pdf.
Повний текст джерелаStanforth, Hannah Amy. "Transcriptional targets of Eph receptor and ephrin signalling in the zebrafish hindbrain." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10053620/.
Повний текст джерелаDolce, Luca. "A DNA-Microarray screening: δ-Catenin, a new mediator of Eph-ephrin signaling". Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-42383.
Повний текст джерелаRohani, Larijani Nazanin. "Characterizing the role of Ephrin Eph signaling on tissue separation in Xenopus Laevis." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=123100.
Повний текст джерелаAu cours du développement embryonnaire, la différenciation cellulaire entraîne lamise en place de frontières nettes afin de séparer les différentes populations decellules qui se dessinent. Plusieurs théories ont tenté d'expliquer ce phénomènefascinant, qui demeure mal compris. La présente étude s'appuie sur la gastrula deXénope afin d'examiner le processus de séparation des tissus aux niveauxcellulaire et moléculaire. A ce stade du développement, des frontières divisentd'abord l'embryon en trois couches de feuillets embryonnaires, puis séparent lanotocorde du mésoderme présomitique. L'imagerie de ces frontières sur descellules vivantes a révélé un mécanisme de répulsion cellulaire, qui serait contrôlépar une combinaison de plusieurs types de récepteurs Eph et de leurs ligands, leséphrines. Nous montrons à la fois par perte et par gain de fonction que leséphrines interagissent avec les récepteurs Eph de manière sélective, et non pasaléatoire. L'expression de ces protéines de part et d'autre des frontières suit unschéma de complémentarité partielle. L'intégration des signaux générés par lespaires d'éphrine-Eph produit une réaction d'amplitude maximale aux interfacesentre les tissus. Nous proposons une simulation numérique de ce phénomène designalisation intégrée, sur la base des concentrations relatives d'éphrines etd'Ephs, ainsi que de leurs affinités de liaison. Cette simulation semble valide pourmodéliser de nombreuses frontières embryonnaires, et ce malgré la variabilité desprofils d'expression des éphrines et Ephs à ces différentes frontières. Nous avonségalement étudié les modifications du cytosquelette en aval de la voie designalisation éphrine-Eph, qui entraîne la contraction cellulaire. Nos résultatsindiquent que les instances de répulsions cellulaires, en conjonction avec lacontraction membrannaire, entravent la formation de liaisons adhésives stablesentre les cellules. Ceci engendre un état d'adhérance faible, se traduisant parl'apparance lisse des Cadhérines le long des frontières embryonnaires. Laprésente thèse apporte une compréhension nouvelle du rôle de la voie designalisation éphrine-Eph dans la régulation des frontières entre différents tissus.Ces trouvailles promettent également d'éclairer l'étude du rôle de ces moléculesdans l'invasion et la métastase de tumeurs.
Falivelli, Giulia <1985>. "Attenuation of Eph Receptor Kinase Activation in Cancer Cells by Coexpressed Ephrin Ligands." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6264/.
Повний текст джерелаPfaff, Dennis. "EphB-ephrinB interactions controlling monocyte and tumor cell adhesion to endothelial cells." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:25-opus-50510.
Повний текст джерелаKöhler, Jenny. "Imaging of the dynamics of Eph receptors and their ephrin ligands in mature hippocampal neurons." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-42068.
Повний текст джерелаNeuber, Christin. "Eph-Rezeptoren und Ephrin-Liganden als molekulare Schnittstelle zwischen Melanomzellen und Tumor-assoziierten inflammatorischen Zellen." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-115913.
Повний текст джерелаAddison, M. E. "Investigating the roles of cell identity regulation and Eph/ephrin signalling in early hindbrain segmentation." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1559130/.
Повний текст джерелаEberhart, Johann. "EphA4/Ephrin interactions in motor axon guidance /." free to MU campus, to others for purchase, 2002. http://wwwlib.umi.com/cr/mo/fullcit?p3060095.
Повний текст джерелаHardy, Katharine. "Regulation of Avian Gastrulation by Fibroblast Growth Factor, Non-Canonical Wnt, and Eph-Ephrin Signaling Pathways." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/195983.
Повний текст джерелаLu, Carole Chih-Chen Bronner-Fraser Marianne. "Cranial neural crest migration in the avian embryo and the roles of Eph-A4 and ephrin-A5 /." Diss., Pasadena, Calif. : California Institute of Technology, 2007. http://resolver.caltech.edu/CaltechETD:etd-10132006-153232.
Повний текст джерелаKadner, Diana. "Mechanism of cell adhesion at the midbrain-hindbrain neural plate in the teleost Danio rerio." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2009. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-23142.
Повний текст джерелаReißenweber, Bettina. "Der Einfluss der Hypoxie auf die Expression und Synthese verschiedener Eph-Rezeptoren und Ephrin-Liganden beim malignen Melanom." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-101756.
Повний текст джерелаEgawa, Miho. "Ephrin B1 is expressed on human luteinizing granulosa cells in corpora lutea of the early luteal phase : the possible involvement of the B-class Eph-ephrin system during corpus luteum formation." Kyoto University, 2005. http://hdl.handle.net/2433/144492.
Повний текст джерелаPicco, Vincent. "Spécification de destinées cellulaires dans l'embryon de l'ascidie Ciona intestinalis : étude de la ségrégation des destinées neurale et notochorde." Nice, 2008. http://www.theses.fr/2008NICE4033.
Повний текст джерелаEarly embryogenesis is a complex process during which diverse cell type precursors are specified in a defined spatio-temporal pattern. Embryos with a fixed cell lineage allow the segregation of cell fates to be precisely followed during embryogenesis. The invertebrate chordate embryos of ascidians are, from that point of view, an ideal model and we are using the ascidian Ciona intestinalis to study how notochord and neural fates become segregated. Using a morpholino knockdown strategy, we have shown that inhibition of ERK1/2 in the neural lineage is mediated by an ephrin membrane-bound ligand, namely ephrin-Ad. Ephrin-Ad is expressed in the animal cells, which are in contact with cells of the neural lineage but not those of the notochord lineage. Using dominant negative forms, we have also shown that this ephrin is mediated via an Eph receptor and the Ci-p120-Ras-GAP, leading to the selective inhibition of ERK1/2 in the neural lineage
Weschenfelder, Markus [Verfasser], and M. [Akademischer Betreuer] Bastmeyer. "Expression rekombinanter Sensoren zur Visualisierung der Oberflächendynamik des Eph/ephrin-Systems in retinalen Wachstumskegeln des Huhns / Markus Weschenfelder. Betreuer: M. Bastmeyer." Karlsruhe : KIT-Bibliothek, 2014. http://d-nb.info/1054397341/34.
Повний текст джерелаKaneko, Megumi. "Cloning and characterization of an Eph receptor and its ligand ephrin in the developing primary olfactory pathway of the moth Manduca sexta." Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/280361.
Повний текст джерелаEvans, Iwan Robert. "Investigating the molecular mechanisms underlying cellular repulsion from ephrin ligands : a potential functional role for the Ena/VASP family downstream of Eph receptors." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432956.
Повний текст джерела竹内, 真吾. "Eph/ephrinシグナルによるRhoファミリーGタンパク質の活性制御メカニズムとその機能の解析". 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/200515.
Повний текст джерелаNeuber, Christin [Verfasser], Jens [Akademischer Betreuer] Pietzsch, Jörg Akademischer Betreuer] Steinbach, and Thomas [Akademischer Betreuer] [Henle. "Eph-Rezeptoren und Ephrin-Liganden als molekulare Schnittstelle zwischen Melanomzellen und Tumor-assoziierten inflammatorischen Zellen / Christin Neuber. Gutachter: Jörg Steinbach ; Thomas Henle. Betreuer: Jens Pietzsch." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://d-nb.info/1068152915/34.
Повний текст джерелаRudolph, Judith [Verfasser], Jürgen [Akademischer Betreuer] Bolz, Christoph [Akademischer Betreuer] Redies, and Dominique [Akademischer Betreuer] Bagnard. "Der Einfluss des Eph/Ephrin-Systems auf die tangentiale Migration cortikaler und striataler Neurone im basalen Telencephalon / Judith Rudolph. Gutachter: Jürgen Bolz ; Christoph Redies ; Dominique Bagnard." Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2014. http://d-nb.info/1047579103/34.
Повний текст джерелаJavier, Fatima Raezelle Santos. "STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1523027075371687.
Повний текст джерелаProtsenko, Anastasiya. "The role of EphB4 and ephrin-B2 interactions in prostate cancer models of intravasation and extravasation." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/118194/2/Anastasiya%20Protsenko%20Thesis.pdf.
Повний текст джерелаBatista, Chary Ely Martin Marquez. "Análise dos mecanismos de neuroplasticidade na porção lombar da medula espinal do rato submetida à lesão isquêmica fototrombótica e tratada pela injeção local de PEDF." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-25042012-093906/.
Повний текст джерелаThe pigment epithelium derived factor (PEDF) is a neurotrophic factor that has a great trophic potential in the motor neurons of the spinal cord, and is able to modulate the lesion microenvironment. We analyzed the capacity of the treatment with PEDF to promote the neuroplasticity after ischemic spinal cord injury. Adult male Wistar rats were underwent to photothrombotic ischemic spinal cord injury, according to the Rose Bengal method, at the level of 11° thoracic segment, and were immediately treated with local injection of PEDF (PEDF group) or solvent (Saline group). Rats underwent to a sham surgery (Sham group) received solvent injection. At the end of surgery, the rats were submitted to neurofunctional tests during 6 weeks. After this period, the animals were euthanized, and the anterior lumbar region of the spinal cord tissue was submitted to immunohistochemistry, western blot and real-time PCR analyses. The inhibitory response of CSPGs, the expression of neurotrophic factors (NT-3, GDNF, BDNF and FGF-2), the molecules associated with angiogenisis and apoptosis (laminin and Bcl-2), the proteins related to neuroplasticity (MAP-2, GAP-43 and synaptophysin), as well the Eph/ephrin system and the RhoA, which is able to modulate the fibers growth, were evaluated. The results showed a spontaneous, and parcial, recovery of the sensory motor behavior of the animals that were underwent to a photothrombotic injury, and the treatment with PEDF was able to potentiate some of these parameters. The analysis of the anterior lumbar region of the spinal cord, caudally to the lesion, showed a decrease of CSPGs, which may have favored the neuroplasticity events. The treatment with PEDF was able to promote the regulation of NT-3 and GDNF, as well the reduction of laminin and the increase of MAP-2 in that region. In relation to the Eph/ephrin system, the ischemic spinal cord injury was able to modulate the EphA4 receptor and ephrin-B1 expression, and the treatment with PEDF possibly regulated the activation state of ephrin-A2 and ephrin-B3 and certainly modulated the ephrin-B2 activation. Eph receptors and ephrins have been found specifically in neurons and astrocytes. Our results confirmed the plastic capacity of the spinal cord after injury and showed that the treatment with PEDF was able to enhance this process
Reißenweber, Bettina Verfasser], Jens [Akademischer Betreuer] Pietzsch, Jörg [Akademischer Betreuer] Steinbach, and Thomas [Akademischer Betreuer] [Henle. "Der Einfluss der Hypoxie auf die Expression und Synthese verschiedener Eph-Rezeptoren und Ephrin-Liganden beim malignen Melanom / Bettina Reißenweber. Gutachter: Jörg Steinbach ; Thomas Henle. Betreuer: Jens Pietzsch ; Jörg Steinbach." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://d-nb.info/1068151196/34.
Повний текст джерелаReißenweber, Bettina [Verfasser], Jens Akademischer Betreuer] Pietzsch, Jörg [Akademischer Betreuer] Steinbach, and Thomas [Akademischer Betreuer] [Henle. "Der Einfluss der Hypoxie auf die Expression und Synthese verschiedener Eph-Rezeptoren und Ephrin-Liganden beim malignen Melanom / Bettina Reißenweber. Gutachter: Jörg Steinbach ; Thomas Henle. Betreuer: Jens Pietzsch ; Jörg Steinbach." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-101756.
Повний текст джерелаCoussens, Anna Kathleen. "Molecular regulation of calvarial suture morphogenesis and human craniofacial diversity." Thesis, Queensland University of Technology, 2007. https://eprints.qut.edu.au/16481/1/Anna_Coussens_Thesis.pdf.
Повний текст джерелаCoussens, Anna Kathleen. "Molecular regulation of calvarial suture morphogenesis and human craniofacial diversity." Queensland University of Technology, 2007. http://eprints.qut.edu.au/16481/.
Повний текст джерелаAshby, Edwina Kingsley. "EphA4 and ephrin-A interactions in avian neural crest cell segmentation." Thesis, 2005. http://hdl.handle.net/2440/61969.
Повний текст джерелаThesis (Ph.D.) -- University of Adelaide, School of Molecular and Biological Sciences, 2005
Bi, Caixia. "Interaction between ephrin/Eph and BDNF in modulating hippocampal synaptic transmission and synapse formation." 2008. http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17436.
Повний текст джерелаAbeynayake, Nethmi. "Role of Eph/ephrin Molecules in Mediating Cross-talk Between Stromal and Neural Populations in the Regulation of Neural Differentiation, Adhesion and Migration." Thesis, 2021. https://hdl.handle.net/2440/135394.
Повний текст джерелаThesis (M.Phil) -- University of Adelaide, Adelaide Medical School, 2021
Çelik, Arzu [Verfasser]. "Restricted and complementary expression patterns of EPH receptors and Ephrin ligands define potential interaction sites in the embryonic and adult olfactory system of zebrafish, Danio rerio / vorgelegt von Arzu Çelik." 2002. http://d-nb.info/964922754/34.
Повний текст джерелаZimmer, Manuel [Verfasser]. "Mechanisms of Eph, ephrin mediated cell-cell communication / eingereicht von Manuel Zimmer." 2003. http://d-nb.info/970032633/34.
Повний текст джерелаBazowski, Jessa. "Characterization of A-type ephrin signaling." Thesis, 2007. http://hdl.handle.net/1828/223.
Повний текст джерелаKrupke, Oliver A. "Cell signaling guides morphogenesis: roles for Eph-Ephrin signaling in sea urchin morphogenesis." Thesis, 2015. http://hdl.handle.net/1828/6443.
Повний текст джерелаGraduate
Bosne, Stéphanie Correia de Matos David 1987. "The Eph/ephrin gene family in the european Amphioxus: an Evo-Devo approach." Master's thesis, 2010. http://hdl.handle.net/10451/2390.
Повний текст джерелаA Evolução e o Desenvolvimento (Evo-Devo) é uma area da biologia que tem por objectivo o estudo e a interpretação de conhecimentos de ambas as areas de evolução e da biologia do desenvolvimento. Tenta assim, explicar e testar as teorias evolutivas ao nivel morfologico. (David 2001) A transição de invertebados para vertebrados é um marco importante na historia evolutiva das especies. A relação filogenética no Filo Chordata é importante para compreender esta transição. O Filo é constituido de tres subfilos Vertebrata, Cephalocordata e Urochordata. As caracteristicas que os une neste Filo é a presença de uma notocorda, um tubo nervoso dorsal, tubo nervoso dorsal, fendas branquiais, um endostélio e uma cauda pós-anal, em pelo menos uma fase de sua vida. Contudo, a relação filogenética dentro do Filo Chordata foi controversa. No século XIX os urocordados foram colocados na base da filogenia do Filo, estando deste modo, os cefalocordados mais proximos dos vertebrados (Fig.1). No entanto, dados moleculares recentes levaram a reversao destas posições estipulando que os cefalocordados se separam antes, localizando-se basalmente ao grupo Urochordata-Vertebrata (Fig.1) (Delsuc 2006). O Filo Cephalochordata compreende dois generos (Branchiostoma and Epigonichtys). O anfioxo (Branchiostoma floridae - especie americana - Branchiostoma lanceolatum -especie europeia) possede uma faringe com fendas branquiais, uma cauda pos anal, um sistema circulatorio ausente de coração e um sistema excretor rudimentar (Fig.2). Contudo carecem de algumas caracteristicas de vertebrado como as células migratorias da crista neural, um endoesqueleto, um cérebro regionalizado e orgãos sensorias pares. Por apresentar um genoma não duplicado, uma copia unica para a maioria das familias multigenicas dos vertebrados, pelas suas caracteristicas morfologicas e do desenvolvimento transitorias aos vertebrados, pela disponibilidade de ferramentas de manipulação génica e vantagens de manutenção em laboratorio e do genoma de Branchiostoma floridae estar completamente sequenciado, o anfioxo é considerado como sendo um bom organismo modelo para estudar a transição de invertebrado a vertebrado. Em 1987, o primeiro receptor de efrina foi clonado. Os receptors (Eph) e ligandos (efn) de efrinas formam a maior das 14 subfamilias de receptores do tipo tirosina kinase. Estas possuem um dominio extracellular N-terminal que permite a interacção com o ligando; um dominio intracelular com funçao de kinase; um dominio SAM; e um dominio PDZ (Fig.4). Os ligandos estão subdivididos em dois grupos, as efnA que se encontram ancoradas à membrana via GPI (glycosylphosphatidylinositol) e as efn B que estão ancoradas por um dominio transmembranar (Fig.4). Os receptores EphA interagem preferencialemente com as efnA e as EphB com as efnB. Esta interacção ligando-receptor tem um papel crucial em processos celulares como a adesão, comunicação, rearranjos de citoesqueleto, divisão, migração, a activação de vias de sinalização citoplasmaticas que promovem a expressão génica. Deste modo, estão implicados em processos de desenvolvimento como a 5 migração das células da crista neural, segmentação e somitogénese, formação de sinapses e proriedades promotoras de tumores. Os receptores e ligandos de efrinas estão presents em todos os Metazoa (de esponjas a vertebrados) em numero (tab. 1), padrões de expressão e funções distintas. Varias das funções desempenhadas pelas efrinas em vertebrados são também encontradas em invertebrados. Foi sugerido que as funções das efrinas teriam evoluido de desempenhar um papel mais simples em processos cellular, ainda mantido em grupos mais basais na filogenia, para papeis mais versateis e diversificados, como os observados em cordados. Neste projecto propusemos um estudo de Evo-Devo da familia de genes das efrinas, pelo seu importante papel no desenvolvimento e pela sua presença em todas as espécies de Metazoa estudadas até a data, usando como modelo experimental o anfioxo europeu, devido à sua posiçao filogenética e caracteristicas. Com o objecctivo de melhor compreender a historia evolutiva e as funções durante o desenvolvimento deste genes os principais passos desenvolvidos foram: i) anotar e descrever os receptores e ligandos de efrinas em Branchiostoma floridae; ii) clonar e sequênciar os genes de efrina na especie europeia Branchiostoma lanceolatum ; iii) elucidar a relação filogenética da familia génica das efrinas em genomas de Metazoa disponiveis (Tab.1) ; iv) determinar os padroes de expressão, em diversos estadios de desenvolvimento, em ambos ligandos e receptores de efrina em Branchiostoma lanceolatum por hibridação in situ. A relação filogenética dos receptores de efrinas esta descrita na Fig.9 desta dissertação e foi realizada com sequências de proteinas no programa Mega4. Nesta analise pode-se verificar que as Eph de vertebrados agrupam-se monofiléticamente juntas. Os genes de cefalocordados estão basais aos de vertebrados, agrupando-se com os dos não-cordados. As Eph de urocordados formam um grupo polifilético, sugerindo a ocorrência de duplicações independentes nesta linhagem, estando CiEphE, CiEphD e CiEphG mais proximos dos vertebrados. Os receptores de efrina dos Cefalocordados parecem ter divergido mais cedo do que os receptores de efrina de urocordados CiEphE, CiEphD and CiEphG, estando de acordo com a topologia proposta por Delsuc (2006) para o Filo Chordata. Os genes de Nematostella vectensis agrupam-se com o outgrupo Ephydatia fluviatilis, sugerindo que esta especie esteve sujeita a duplicaçoes independentes. A topologia obtida para os ligandos de efrina esta representada na Fig.10. É de notar que os ligandos dos vertebrados formam dois grupos monofiléticos distintos, um que agrupa as efnA e outro as efnB. As efnA de vertebrados parecem estar filogenéticamente mais proximas das efnA de urocordados (CiefnAa, CiefnAb, CiefnAc and CiefnAd) e efnB mais proximas das efn de cefalocordados (Bfefn1, Bfefn2 e Bfefn3). Tal como observado com os receptors, os ligandos dos não-cordados formam um grupo monofilético. O estudo da expressão dos receptores (BlEph1 e BlEph2) e ligandos (Blefn1 e Blefn2) de efrina foi feita pela técnica de hibridação in situ em embriões de Branchiostoma lanceolatum durante varios estadios de desenvolvimento (morulas de 32 celulas até larvas de 60horas). No estadio de morula todos os genes expressam-se no embrião inteiro. 6 Durante a neurulação BlEph1 expressava-se na mesoderme lateral, nos somitos em formação e possivelmente no precursor da vesicular cerebral. Na neurula tardia encontrava-se expresso na notocorda e no tubo neural e na future região oral. No estadio de pré-boca expressava-se na notocorda anterior e posterior, na boca e faringe em formação. No estadio de larva este gene expressava-se na notocorda anterior e posterior, na vesicular cerebral, na boca, no endostélio, na glandula club-shaped, no diverticulum. (Fig.11) Durante a gastrulação, BlEph2 parecia expressar-se em todos os tecidos. Um padrão segmentado parecia aparecer durante a neurulação que parece seguir o padrão dos somitos em formação. No estadio de pré-boca BlEph2 expressava-se na boca em formação e na notocorda anterior. Nas larvas a expressão deste gene parecia localizar-se na boca e na região da faringe. (Fig.12) O padrão de expressão dos ligandos de efrina (Blefn1 e Blefn2) parecia estar de acordo com o padrão observado nos receptores. Em gastrulas Blefn1 expressava-se maioritariamente na mesoderme justo ao blastoporo. Durante a neurulação a expressão era mesodermica, junto ao fecho do tubo neural e também parecia expressar-se em populacões de neuronios. No estadio pré-boca parecia expressar-se na futura região oral, na notocorda posterior e a endoderme posterior. No estado de larva a expressão parecia mais restringida a zona da boca e da faringe, mas ligeiramente expresso nos restantes tecidos, exceptuando a vesicula cerebral. (Fig.13) Durante a gastrulação Blefn2 parecia expressar-se na gastrula inteira. Durante a neurulação a expressão parecia restringida a mesoendoderme, exceptuando o dominio mais posterior. Em embriões pré-boca parecia localizar-se na região da faringe em formação, na glandula de muco e na notocorda posterior. Em larvas a expressão parecia localizar-se na região da boca e da faringe e também na notocorda posterior (Fig.5F). Na literatura esta descrito que as efrinas expressam-se em cordados nas zonas dos somitos em formação, na notocorda, no tubo neural, na mesoderme paraxial e nos nervos perifericos, como demonstrado pelas imagens obtidas por hibridação in situ (Fig.11 a 14). Em vertebrados estes genes também participam na formação de varias estruturas faciais incluido a região oral e os seus padrões de inervação, padrão também observado nos receptores e ligandos de efrinas de Branchiostoma lanceolatum sugerindo a co-opção destes genes para esta função durante o desenvolvimento em Chordados (Fig.11-14). Com este trabalho foi possivel elucidar algumas das questoes sobre a expressão e a posição filogenética dos membros da familia genica das efrinas no anfioxo europeu (Branchiostoma lanceolatum). A estrutura destes genes parece ser conservada desde as esponjas aos vertebrados, mas também as funções desempenhadas durante no desenvolvimento. Entre estes incluem-seos processos a nivel cellular que, ao longo da evolução sofreram fenomenos de complexificação, na transição para cordados. Adicionado a estas observações, a topologia filogenética sugere fenomenos de co-opção para as novas funçoes de duplicações especificas de linhagem. Existem também evidências para convergência evolutiva entre espécies e de evolução paralela dentro da mesma espécie. Os cefalocordados parecem ocupar, relativamente a esta analise, uma posição entre os não-cordados e os vertebrados o que suporta a nova filogenia sugerida por Delsuc et al em 2006. No geral, pode-se sugerir que os genes da familia das efrinas diversificaram varias vezes ao longo da evolução dos 7 Metazoa e também que o ancestral dos urocordados e vertebrados apresentaria um unico receptor de efrina e dois ligandos. Contudo, dados adicionais sobre as funções, padrões de expressão génica e filogenia dos Metazoa seriam necessarios para melhor estabelecer uma relação evolutiva da familia génica das efrinas e o seu papel durante a evolução.
The Ephrin receptor and ligand gene families are implicated in several cellular processes such as cellular adhesion, communication, division, migration, and compartmentalization. These play an important role in development including, for instance, neural crest cell migration, somitogenesis, axon guidance, and have even been shown to have tumor promoting properties. They are described to be present from sponges to vertebrates in multiple copies, maintaining a conserved genomic structure. Cephalochordates, recently placed at the base of the Chordata, are considered to be the living animal that best approximates the ancestor at the transition from invertebrates to vertebrates. The phylogenetic analysis of this project shows that Eph and efn families have been independently expanded in amphioxus, vertebrate, and other Metazoan clades suggesting that each have convergently evolved complex Eph/efn complements. In the European amphioxus (Branchiostoma lanceolatum) the Eph/ephrin gene family seems to express mostly in the forming mouth apparatus, somites and notochord, as assessed by whole-mount in situ hybridization (ISH). The Eph/ephrin ISH expression pattern corresponds to some vertebrate characteristics for these genes, but they are also implied in several cellular processes similarly to invertebrates. In spite of the evidence, it is difficult to assess the exact evolutionary relationship and developmental role of these genes in amphioxus with these data, or to extrapolate to Metazoa.
Wiedemann, Elisa. "Einfluss von ephrin-A1 auf das Proliferations- sowie Migrationsverhalten von Endothelzellen." 2018. https://tud.qucosa.de/id/qucosa%3A35456.
Повний текст джерелаThe Eph-family represents the largest subgroup of tyrosine kinase receptors. Both the Eph-receptors and the ephrin-ligands are membrane-associated proteins whose interaction is a way of contact-dependent communication that influences a wide variety of cellular functions. In scientific research the Eph-family is known for its impact on developmental and tumour-biology, whereas the role of Eph-receptors and ephrin-ligands in atherosclerosis and repair mechanisms is still not well understood. The aim of the present study was to examine the influence of the ligand ephrin-A1 and its interaction with its receptor EphA2 on endothelial proliferation and migration by performing cellcultural experimentation using HUVEC and HUAEC.:INHALTSVERZEICHNIS I ABKÜRZUNGSVERZEICHNIS V ABBILDUNGSVERZEICHNIS IX TABELLENVERZEICHNIS XI 1 EINLEITUNG 1 1.1 Die Rolle des Endothels in der Atherosklerose 1 1.2 Die Migration von Endothelzellen 6 1.3 Die Eph-Familie 9 1.4 Potentielle Funktionen der Eph-Familie in der endothelialen Proliferation und Migration 14 1.5 Zielstellung der Arbeit 16 2 MATERIAL 17 2.1 Geräte 17 2.2 Zellkulturmaterial 18 2.3 Verwendete Kulturmedien 18 2.4 Verwendete Zelllinien und E. coli Stämme 19 2.5 Verwendete Kit-Systeme 19 2.6 Verwendete Oligonukleotide 20 2.7 Verwendete Plasmide 21 2.8 Konstruierte Plasmide 23 2.9 Chemikalien 23 2.10 Puffer, Gele, Lösungen 23 3 METHODEN 24 3.1 Zellbiologische Methoden 24 3.2 Proteinbiochemische Methoden 28 3.3 Molekularbiologische und gentechnische Methoden 32 3.4 Scratch Assay 44 3.5 Beurteilung der Zellproliferation mittels BrdU-Inkorporation 44 3.6 Wundheilungsassay 45 3.7 Migrationsassay 48 3.8 Baculovirale Talin-RFP- und Aktin-GFP-Expression 49 3.9 Datenanalyse und statistische Auswertung 49 4 ERGEBNISSE 50 4.1 Molekularbiologische und proteinbiochemische Charakterisierung verschiedener Eph/ephrine in proliferierenden Endothelzellen 50 4.2 Molekularbiologische Charakterisierung von ephrin-A1, EphA2 und EphA4 unter Kontaktinhibition in HUVEC 56 4.3 Einfluss eines Zellzyklusarrests auf die Expression verschiedener ephrin-Liganden und Eph-Rezeptoren in Endothelzellen 58 4.4 Hemmung von ephrin-A1 und EphA2 mittels siRNA 63 4.5 Einfluss einer siRNA-vermittelten Hemmung von ephrin-A1 und EphA2 auf die Proliferation von HUVEC 65 4.6 Überexpression von ephrin-A1 mittels eines adenoviralen Vektors 67 4.7 Einfluss einer Überexpression von ephrin-A1 auf die Proliferation von HUVEC 68 4.8 Reinitiation von Proliferation und Migration in HUVEC mittels Scratch Assay 69 4.9 Einfluss der Modulation des ephrin-A1- sowie EphA2-Gehaltes auf das Wundheilungsverhalten von HUVEC 73 4.10 Charakterisierung des Migrationsverhaltens von HUVEC unter veränderter ephrin-A1-Expression mittels live cell imaging 75 4.11 Einfluss einer veränderten ephrin-A1-Expression auf den EphA2-Phosphorylierungsstatus 78 4.12 Grenzzonenverhalten von HUVEC an ephrin-A1-beschichteten Oberflächen 80 4.13 Fluoreszenzmikroskopische Charakterisierung fokaler Adhäsionen und des Aktin-Zytoskelettes unter modulierter ephrin A1 Expression 81 5 DISKUSSION 84 5.1 Die Eph-Familie im Kontext der Reendothelialisierung 84 5.2 Einfluss des Eph/ephrin Systems auf das Proliferationsverhalten von Zellen 86 5.3 Auswirkungen einer ephrin-A1-EphA2-Wechselwirkung auf die Proliferation 90 5.4 Einfluss der Eph-Familie auf die zelluläre Migration und Wundheilung 93 5.5 Zusammenfassende Betrachtung und Ausblick 106 6 ZUSAMMENFASSUNG 109 6.1 In deutscher Sprache 109 6.2 In englischer Sprache 111 7 LITERATURVERZEICHNIS 113 8 DANKSAGUNG 133 9 ANHANG 134 10 ERKLÄRUNGEN 138 10.1 Erklärungen zur Eröffnung des Promotionsverfahrens 138 10.2 Erklärung über die Einhaltung der aktuellen gesetzlichen Vorgaben im Rahmen der Dissertation 140
Mellott, Daniel Owen. "Regulation of avian cranial neural crest cell migration by eph receptors and ephrin ligands." Thesis, 2006. http://hdl.handle.net/1828/978.
Повний текст джерелаPeng, Pin-Han, and 彭品涵. "Investigating the role of Plexin A, Semaphorin 2a, MICAL-like, Eph and Ephrin during Drosophila oogenesis." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/325j44.
Повний текст джерела