Dissertations / Theses on the topic 'Notch'
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Maxe, Liza, Kiana Entezarjo, and Douglas Karegren. "Swap Notch." Thesis, Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-40654.
Full textQuillard, Thibaut. "Importance de la voie Notch dans la dysfonction endothéliale en transplantation : régulation et fonctions des récepteurs Notch2 et Notch4." Nantes, 2008. https://archive.bu.univ-nantes.fr/pollux/show/show?id=6bdde4e3-76bb-4a01-9661-3ee28931b379.
Full textNotch plays major roles in endothelial cells (EC) survival, proliferation and transdifferentiation. These events are particularly implicated in transplant arteriosclerosis (TA). This work aims to define Notch molecules regulation and its functional relevance in graft EC. We first studied Notch family members (receptors, ligands and effectors) regulation during EC activation by cytokines. We show that TNFα induced a switch in Notch expression pattern by a strong down-regulation of Notch4 and an increase in Notch2, respectively dependent on NFkB and PI3K pathways. This effect is associated with a global decrease in CBF1 activity and an opposite regulation of hes1 and hey1. Decrease in EC-restricted Notch4 expression is also associated with TA in a rat cardiac allograft model where TNFα, TGFβ and IL10 are strongly expressed. Inhibition of Notch4 and hes1 by siRNA enhances VCAM1 expression, induces apoptosis and impairs endothelial injury repair, suggesting that Notch4 expression is required to maintain EC survival and quiescence. To study the role of Notch2 in EC, we constructed a recombinant adenovirus for Notch2ICD (N2ICD). Constitutive expression of N2ICD leads to EC apoptosis associated with a drastic repression of pro- (survivin, april) and anti-apoptotic genes (bim, DAPK2, HRK, DR5, CD40). Effect of N2ICD is mainly dependent on survivin inhibition. Accordingly, Notch2 knock-down increases survivin expression and protects EC from anoïkis. Altogether, our results reveal crosstalks between TNF and Notch signaling during endothelial dysfunction, propose a role for Notch4 in preventing TA-related EC dysfunction and for Notch2 role in EC survival through survivin regulation
Huang, Yuchen. "Adaptive Notch Filter." PDXScholar, 1994. https://pdxscholar.library.pdx.edu/open_access_etds/4802.
Full textO'Neill, Christine F. "Notch Regulation of Human Breat Cancer Progression: Contrasting Roles for Notch Signaling." Fogler Library, University of Maine, 2007. http://www.library.umaine.edu/theses/pdf/O'NeillCF2007.pdf.
Full textPoudel, Rajeeb. "Single Notch Versus Multi Notch Credit Rating Changes and the Business Cycle." Thesis, University of North Texas, 2015. https://digital.library.unt.edu/ark:/67531/metadc848118/.
Full textSerafin, Valentina. "Notch3 signalling promotes tumour growth in colorectal cancer: implication for Notch target therapy." Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422188.
Full textE’ ormai noto da alcuni anni che un’aberrante attivazione della via di segnalazione di Notch gioca un ruolo critico nella patogenesi della leucemia linfoblastica acuta a cellule T (T-ALL) e di alcune neoplasie solide come il cancro del polmone, della mammella e dell’ovaio. Inoltre, una marcata attivazione del recettore Notch1 è stata osservata negli adenomi intestinali ed è correlata all’aumentata espressione del ligando Jagged-1 indotta dall’attivazione del pathway Wnt-APC-β-catenina. E’ stato inoltre dimostrato che questa pathway, insieme a quella di Notch, interviene nella regolazione della proliferazione e del differenziamento delle cellule epiteliali della mucosa intestinale normale. Attualmente, non si sa ancora se altri meccanismi di attivazione della pathway di Notch, oltre a quello ligando-dipendente, siano operativi nel CRC e nemmeno se possano essere coinvolti altri recettori della stessa famiglia. In questo studio, abbiamo cercato di chiarire il possibile coinvolgimento di Notch3 nel CRC. Basandoci sull’osservazione che Notch3 risulta essere frequentemente overespresso sia a livello di mRNA che di proteina nei campioni umani di CRC, abbiamo cercato di chiarire come il recettore Notch3 potesse modulare le proprietà tumorigeniche delle cellule di CRC. A tale scopo, si sono rivelati particolarmente utili alcuni xenotrapianti di cellule umane di CRC che presentano una diversa aggressività in topi NOD/SCID. Infatti, utilizzando i tumori sperimentali, abbiamo potuto dimostrare che l’espressione dei diversi componenti del pathway di Notch risulta essere significativamente elevata nella variante aggressiva rispetto a quella dormiente. In particolare si è osservata un’ aumentata espressione dei ligandi DLL4 e Jagged-1 ed un incremento dei livelli del trascritto di Notch3 e della forma attiva del recettore nei tumori che crescono più rapidamente. Una simile up-regolazione di Notch3 con un’aumentata attivazione della via di segnalazione si è osservata in seguito a stimolazione delle cellule di CRC in vitro con il ligando DLL4 ricombinante. Analogamente, anche l’overespressione di una forma attiva del recettore Notch3 in queste stesse cellule conferisce loro una maggiore capacità proliferativa e favorisce la formazione di tumori in vivo. Al contrario, si è visto che l’inattivazione del pathway mediante silenziamento genico di Notch3 nelle cellule aggressive di CRC, determina significative alterazioni del ciclo cellulare con conseguente riduzione nella proliferazione in vitro e un ritardo nella crescita dei tumori in vivo. Complessivamente, questi risultati dimostrano che il recettore Notch3 può modulare le proprietà tumorigeniche delle cellule di CRC, in particolare contribuendo a mantenere elevata l’attivazione della via di Notch nei tumori esprimenti nel loro microambiente tumorale alti livelli di DLL4. Inoltre, l’inoculo della variante più aggressiva rispetto a quella dormiente per via endovenosa in topi NOD/SCID ha mostrato che le cellule di CRC non hanno solo una diversa capacità tumorigenica, ma anche una differente capacità metastatica a livello polmonare, sia in termine di numero che di dimensioni delle metastasi osservate. Basandoci sui risultati fin qui ottenuti, e su uno studio recentemente pubblicato in cui è stato dimostrato come il pathway di Notch sembra essere coinvolto anche nel processo di metastatizzazione, abbiamo condotto un primo esperimento pilota che prevedeva, in topi portatori di metastasi polmonari, il blocco dei recettori Notch3 e Notch2 mediante l’impiego di un anticorpo neutralizzante. Sfortunatamente i risultati ottenuti non hanno fino ad ora mostrato una riduzione significativa nel numero e nelle dimensioni delle metastasi analizzate: l’analisi dei livelli di alterazione di Notch dopo il trattamento è in corso. A conclusione dello studio le nostre osservazioni rappresentano un punto di partenza per un futuro sviluppo di terapie che abbiano Notch3 come bersaglio per il trattamento di un sottogruppo di casi di CRC.
Rangarao, Kaluri Venkata. "Adaptive digital notch filtering." Thesis, Monterey, California. Naval Postgraduate School, 1991. http://hdl.handle.net/10945/26345.
Full textSingh, Nita. "The expression of the Notch receptors, Notch ligands, and the Fringe genes in hematopoiesis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq29262.pdf.
Full textFerreira, António Carlos Ribeiro. "Notch signaling pathway in gastric carcinogenesis: E-cadherin inactivation on Noth-dependent cell survival." Doctoral thesis, Faculdade de Medicina da Universidade do Porto, 2010. http://hdl.handle.net/10216/55364.
Full textFerreira, António Carlos Ribeiro. "Notch signaling pathway in gastric carcinogenesis: E-cadherin inactivation on Noth-dependent cell survival." Tese, Faculdade de Medicina da Universidade do Porto, 2010. http://hdl.handle.net/10216/55364.
Full textPrexl, Andrea. "Der Notch-Signaltransduktionsweg in Hydra." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-119290.
Full textOrtica, Sara. "Notch pathway in liver progenitors." Paris 7, 2012. http://www.theses.fr/2012PA077175.
Full textNotch signalling is a highly conserved pathway that mediates short-range communications inter-cells. In mammals, four Notch receptors (Notch 1-4) are present. The receptor stands as a transmembrane heterodimer at the cell surface and it is activated after the interaction with a ligand. After a series of cleavages the activated form of the receptor (Nie) is translocated into the nucleus, where it activates target gene transcription. To get a better insight into the mechanisms of Notch function in liver progenitors we chose to use an in vitro System based on Bipotential Mouse Embryonic Liver (BMEL) cells. These progenitors can be maintained in the undifferentiated state or differentiated into hepatocytes or cholangiocytes. Our results show that Notch is active in undifferentiated BMEL cells, and that its inhibition decreases BMEL cell proliferation in a dose-dependent manner, through inhibition of S phase entry. Nic2 and Nic4 can complement the inhibition on proliferation, while Nic3 impairs proliferation and increases multinucleation. Moreover, we find that Nic3 is conducive of hepatocytic specification, while the other Notch receptors inhibit this fate. In conclusion, we show that the four Notch receptors have non-redundant roles during liver development, and that the type of the receptor involved can be more important than the overall pathway activation. Finally, we tested the effects of Numb, a Notch inhibitor upregulated upon hepatocytic commitment. Expression of Numb in undifferentiated progenitors reduces their proliferation rate, and induces a hepatocyte-like phenotype with large and multinucleated cells expressing hepatocytic markers
Jangsri, Venus. "Infinite impulse response notch filter." Thesis, Monterey, California. Naval Postgraduate School, 1988. http://hdl.handle.net/10945/23269.
Full textA pipeline technique by Loomis and Sinha has been applied to the design of recursive digital filters. Recursive digital filters operating at hitherto impossibly high rates can be designed by this technique. An alternate technique by R. Gnanasekaran allows high speed implementation using the state-space structure directly. High throughput is also achieved by use of pipelined multiply-add modules. The actual hardware complexity will depend upon the number of pipeline stages. These techniques are used for the design of the I IR notch filter and finally, a comparison of the performance and complexity of these two techniques is presented.
http://archive.org/details/infiniteimpulser00jang
Lieutenant, Royal Thai Navy
Thomas, James W. "Efficient narrow-band notch filter." Master's thesis, This resource online, 1994. http://scholar.lib.vt.edu/theses/available/etd-02022010-020151/.
Full textJaekel, Robert. "Regulation des Notch-Signalweges durch Lethal (2) giant discs (Lgd) und durch die Notch-Liganden." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=983735255.
Full textSchüller, Martina. "Biochemische Charakterisierung der humanen Notch 1 und Notch 3 Rezeptoren und Analyse der Expression des humanen Notch 1 Rezeptors auf Zell-Linien und histologischen Präparaten." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-60321.
Full textBenson, Robert A. "Notch and CD4+ T cell function." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/25108.
Full textPetersson, Johan. "Notch signaling pathways inthe obese mouse." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-66818.
Full textKarlström, Helena. "Notch receptor processing and CNS disease /." Stockholm : [Karolinska institutets bibl.], 2002. http://diss.kib.ki.se/2002/91-7349-300-7/.
Full textGlittenberg, Marcus Thorleiv. "Serrate mediated regulation of Notch signalling." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614149.
Full textBeggs, Barry John. "Notch signalling and B-cell activation." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619856.
Full textHousden, B. "Notch targets and EGFR pathway regulation." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604264.
Full textNichols, II James Tucker. "DSL-ligand endocytosis and notch signaling." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1692099791&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full textDeftos, Michael Laing. "Notch signaling in T cell development /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/8364.
Full textUbezio, B. "Notch signalling dynamics during sprouting angiogenesis." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1420272/.
Full textGiovannini, Catia <1975>. "Ruolo dei geni Notch nell'epatocarcinoma umano." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/196/1/TESI.pdf.
Full textGiovannini, Catia <1975>. "Ruolo dei geni Notch nell'epatocarcinoma umano." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/196/.
Full textMOREL, VERONIQUE. "Mecanismes moleculaires de la voie de signalisation notch. Etude de la regulation de single-minded par notch." Paris 6, 2001. http://www.theses.fr/2001PA066173.
Full textPigatti, Fernanda Mombrini. "Participação da via Notch em lesões labiais fotoinduzidas." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-08082016-104155/.
Full textThe intense exposure to the sun subject the lips, particularly the lower, the damage caused by the absorption of ultraviolet (UV) radiation. The squamous cell carcinoma is a malignant tumor that develops on the lips after prolonged chronic exposure to UV rays and it is believed that all cases are preceded by potentially malignant disorder called actinic cheilitis. Both lesions are caused by the harmful effects of UV radiation acting directly on the DNA, through the phenomenon of photocarcinogenesis. In this process, the radiation causes mutations that are capable of causing the initiation, progression and promotion of cancer. However, it is also important to consider that other molecular events, apart from the mutations are involved in the initiation and progression of cancer. Molecular abnormalities with gain or loss of Notch pathway components function are involved in several types of hematological and solid cancer. However, the participation of Notch signaling in lip cancer is still unknown. The objective of this study was to investigate whether the Notch pathway is related to injuries actinic cheilitis and squamous cell carcinoma of the lip and participation in oral photocarcinogenesis. For this, were used 45 cases of actinic cheilitis, 15 cases of squamous cell carcinoma of the lip and lip 05 cases with normal aspect in which we analyzed the expression of Notch1 and Jagged1 by immunohistochemistry. The results showed loss of Notch1 expression in 40% of squamous cell carcinomas of the lip, suggesting that reduced expression of Notch1 can convert to an activated keratinocytes and immature state. There was also a difference in labeling patterns of Notch 1 and Jagged1 epithelial cells suggesting that the Notch pathway signal is transmitted from an apical cell to a basal cell due to localization of cells expressing the receptor and expressing the ligand. In summary, the immunohistochemical results do not show a differential regulation of Notch 1 and Jagged1 expression in UV induced lesions.
Hofmann, Jennifer Jean. "Notch signaling in vascular development the roles of notch 1 and jagged 1 in vessel morphogenesis and disease /." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1925779381&sid=21&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full textLehar, Sophie M. "Tuning Notch signals in T cell development /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/8356.
Full textMoretti, Julien. "Déubiquitinations dans la voie de signalisation Notch." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2011. http://tel.archives-ouvertes.fr/tel-00726110.
Full textBeatus, Paul. "Molecular diversity in the Notch receptor family /." Stockholm : Karolinska Univ. Press, 2001. http://diss.kib.ki.se/2001/91-89428-20-x/.
Full textDavati, Soheil. "VLSI implementation of recursive digital notch filter." Ohio : Ohio University, 1986. http://www.ohiolink.edu/etd/view.cgi?ohiou1183128831.
Full textCollins, S. M. "Notch targets in the Drosophila hematopoietic system." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597869.
Full textJohnson, R. I. "Intersections between Notch signalling and planar polarity." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605640.
Full textTay, Joyce Z. Y. "Structural Studies Of Notch And Its Ligands." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504619.
Full textOon, Chern. "Role of Notch ligands in tumour angiogenesis." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:cb237fdd-e532-406c-808b-8092257968c2.
Full textMurta, Daniel José de Moura Carita Dinis. "Notch signaling, genital remodeling and reproductive function." Doctoral thesis, Universidade de Lisboa. Faculdade de Medicina Veterinária, 2014. http://hdl.handle.net/10400.5/6889.
Full textThe objective of this thesis is to evaluate the association between Notch signaling, genital cellular remodeling and reproductive function, in the mouse model. Five experimental chapters are included in this thesis. In experiments 1 and 2, we evaluated transcription and expression patterns of Notch component and effector genes in testis post-natal development, along the spermatogenic cycle and the epididymis. In experiment 3, we evaluated the male reproductive phenotype of in vivo Notch blockade by DAPT. In experiments 4 and 5 we evaluated transcription and expression patterns of Notch component and effector genes in the ovary, oviduct and uterus along the estrous cycle. Results indicate that Notch signaling is active and associated to male and female genital cellular remodeling. In the male, results prompt for a regulatory role of Notch signaling in spermatogonia pool maintenance, onset of spermatogenesis, in the pace of the spermatogenic cycle, germ cell identity, and epididymis spermatozoa maturation. In the female, results prompt for a regulatory role in ovarian follicle and corpus luteum development, and oviduct and uterus epithelial cell turnover and function. Notch signaling is operating in the testis and ovarian cellular interstitium, and in luminal and glandular epithelia of genital tract, probably regulating intercellular communication.
RESUMO - A via de sinalização Notch, remodelação celular genital e a função reprodutiva. - Esta tese avalia a relação entre a via de sinalização Notch, o remodelação celular genital e a função reprodutiva, sendo constituída por cinco capítulo experimentais. Nos dois primeiros, avaliamos o padrão de transcrição e expressão dos componentes e efectores da via Notch no desenvolvimento testicular pós-natal, ao longo do ciclo espermático e no epidídimo. Na experiência 3, avaliamos o fenótipo reprodutivo masculino decorrente do bloqueio in vivo da via Notch por DAPT. Nas experiências 4 e 5 analisamos o padrão de transcrição e de expressão dos componentes e efectores da via Notch no ovário, oviduto e no útero ao longo do ciclo éstrico. Os resultados indicam que a via Notch está activa e associada à remodelação genital masculino e feminino. No macho, os resultados apontam-lhe um papel regulador na manutenção do pool de espermatogónias, no início da espermatogénese, na coordenação do ciclo espermático, na identidade celular germinal, e na maturação espermática. Na fêmea, os resultados apontam para um papel regulador no desenvolvimento folicular e do corpo lúteo, e na função e ciclicidade do oviduto e útero. A via Notch opera no interstício celular do testículo e do ovário, e no epitélio luminal e glandular do tracto reprodutivo, regulando a comunicação intercelular.
Jones, Matthew Leslie. "The subnuclear localisation of Notch responsive genes." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274909.
Full textMoretti, Julien. "Deubiquitinations dans la voie de signalisation Notch." Paris 6, 2011. http://www.theses.fr/2011PA066365.
Full textEdwards, Robert Tyler. "Performance of a Biomimetically Inspired Notch Design." University of Dayton / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1462039449.
Full textHernandez, de Madrid Diaz Beatriz. "Structural basis of serrate regulation of Notch." Thesis, University of Manchester, 2009. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.518890.
Full textLaddada, Lilia. "Etude du développement des tendons et de leur interaction avec les précurseurs de muscles lors de la myogenèse appendiculaire chez la Drosophile." Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAC011/document.
Full textThe formation of the musculo-(exo)skeletal system in drosophila is a remarkable example of tissue patterning making it a suitable model for studying multiple tissue interactions during development.The aim of our study is to better understand appendicular myogenesis through the identification of early interactions between tendon and muscle precursors, and by investigating the mechanisms governing the specification of tendon cell precursors of the leg disc. In order to characterize the interaction between these two tissues, we adapted the GRASP method (GFP Reconstitution Across Synaptic Partners) and set up live imaging experiments to reveal cellular interactions between tendon precursors and myoblasts. We have also conducted a genome wide cell-specific analysis using Fluorescence-activated cell sorting (FACS) on imaginal discs which allowed us to perform a tendon cell specific transcriptional analysis.To test whether reciprocal muscle-tendon interactions are necessary for correct muscle-tendon development, I performed experiments to specifically interfere with the development of tendon or muscle precursors. By altering tendon precursors formation during the early steps of leg development, we affect the spatial localization of the associated myoblasts. These findings provide the first evidence of the developmental impact of early interactions between muscle and tendon precursors in the leg disc.In the second part of my project, I investigated the role of Notch pathway and odd-skipped genes in the differentiation and morphogenesis of tendon precursors. Thus, I have demonstrated that Notch signalling pathway is necessary and locally sufficient for the initiation of stripe expression, and that both odd-skipped genes and stripe are required downstream of Notch to promote morphological changes associated with formation of long tubular tendons
Boroumand, Soulmaz. "Investigating the epidermal Notch activation during wound healing and the consequences of prolonged Notch activity during skin wound healing." Thesis, Durham University, 2014. http://etheses.dur.ac.uk/10785/.
Full textKobia, F. M. "TARGETING NOTCH TRAFFICKING IN HUMAN CANCER CELLS: A. PHARMACOLOGIC INHIBITION OF THE VACUOLAR H+ ATPASE REDUCES PHYSIOLOGIC AND ONCOGENIC NOTCH SIGNALING. B. HIGH CONTENT SCREEN FOR NOVEL MODULATORS OF THE NOTCH PATHWAY." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/365255.
Full textOltmann, Meredith Leigh. "Disruption of the furin cleavage site in mouse Notch 1 results in cardiovascular malformations due to hypomorphic Notch 1 signaling." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1872078271&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full textShaw, Benjamin. "Function and evolution of the atypical Notch ligands Dlk1 and Dlk2 during vertebrate development." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/271791.
Full textMasià, Fontana Anna. "El papel de la vía Notch en Rabdomiosarcoma." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/121513.
Full textRhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma in children. Patients with metastatic RMS continue to have very poor prognosis. This work provides evidence of Notch pathway expression and activation in RMS and it demonstrates a critical role of the Notch pathway in the activation of the process that leads to cell mobility and invasiveness in RMS cells. Furthermore N- cadherin and α9-integrin are postulated as leading actors in the association between the Notch pathway and promotion of cell adhesion, motility and invasion, pointing to these proteins and the Notch pathway itself as interesting putative targets for new molecular therapies against metastases in RMS. It also describes the observed effects of the inhibition of the Notch pathway in vivo.
Guiu, Sagarra Jordi 1983. "Notch activation and downstream targets in embryonic hematopoiesis." Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/98475.
Full textThe aorta-gonad-mesonephros (AGM) is the first Hematopoietic Stem Cell (HSC) niche. It was previously shown that Notch pathway is required to induce the arterial fate as well as to generate Hematopoietic Stem Cells. HSC emerge at the site of arterial vessels during embryonic development. Since arterial fate precedes HSC generation, it has long been controversial whether Notch exclusively induces the arterial program and the lack of HSC is a secondary defect; or Notch is directly involved in activating both genetic programs, arterial and hematopoietic. The best-characterized Notch targets are Hes and Hesrelated genes (Hrt) since they are involved in most of described Notch functions, however there is a growing number of tissue-specific transcriptional Notch-targets. In this thesis, we found that Jagged-mediated activation of Notch is required for the correct execution of the definitive hematopoietic program but not for the establishment of the arterial fate, thus demonstrating that Notch exerts a specific hematopoietic function in the embryo. Downstream of Notch pathway, we also show that embryos deficient for Hes1 and Hes5 alleles contain an intact arterial program but produce increased numbers of non-functional hematopoietic stem cells associated to higher levels of the hematopoietic regulators Runx1, Myb and Gata2. Moreover, Gata2 transcription is positively regulated by Notch and negatively controlled by HES-1. This creates an incoherent feed-forward loop that tightly controls Gata2 levels to generate HSC.