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Transcriptional control in the context of primary neurogenesis

dc.contributor.advisorPieler, Tomas Prof. Dr.de
dc.contributor.authorKlisch, Tiemode
dc.date.accessioned2013-01-22T15:33:59Zde
dc.date.available2013-01-30T23:51:04Zde
dc.date.issued2006-09-18de
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-000D-F109-Fde
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-3376
dc.description.abstractDas Myc/Max/Mad Netzwerk von bHLH-Zip Transkriptionsfaktoren spielt wesentliche Rollen während verschiedenster zellulärer Prozesse wie Proliferation, Differenzierung und Apoptose. Mxi1, ein Mad Familienmitglied, wurde in unserem Laboratorium auf der Grundlage von seinem Expressionsmusters in den Territorien der primären Neurogenese isoliert. Im ersten Teil der Dissertation wurde eine funktionelle Charakterisierung von Xmxi1 während der Xenopus Embryogenesis durchgeführt. Übereinstimmend mit einer frühen Rolle in der Neurogenese wurde Xmxi1 positive durch panneurale und pro-neurale Gene, sowie negativ durch den Notch-Signalweg reguliert. Loss-of-Function Experimente demonstrierten eine wesentliche Rolle für Xmxi1 in der Entwicklung primärer Neuronen. Überexpression von Xmxi1 resultiert in einer vorübergehenden Hemmung der primären Neurogenese, doch in späteren Stadien können ektopische Neuronen nachgewiesen werden. Während der primären Neurogenese, schränkt der Notch-Signalweg die Zahl der primären Nervenzellen ein. Im zweiten Teil der Dissertation, wurde ein Durchmusterung einer cDNA Bank vorgenommen, um frühe Zielgene des Notch-Effektors ESR1 zu identifizieren. Eine in frühen ESR1-Zielgenen bereicherte cDNA Bibliothek wurde dafür hergestellt mittels Überexpression von einem Hormon-induzierbaren, aktivierenden ESR1 Konstrukt (ESR1-VP16-GR). Insgesamt wurden 55 gene identifiziert, die ESR1 Zielgene sein könnten.de
dc.format.mimetypeapplication/pdfde
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/de
dc.titleTranscriptional control in the context of primary neurogenesisde
dc.typedoctoralThesisde
dc.title.translatedTranskriptionale Regulation während der primären Neurogenesede
dc.contributor.refereeriegelstein, Kerstin Prof. Dr.de
dc.date.examination2006-09-07de
dc.subject.dnb500 Naturwissenschaftende
dc.subject.gokWKF 300de
dc.description.abstractengThe Myc/Max/Mad network of bHLH-Zip transcription factors plays an essential role in a variety of cellular processes including proliferation, differentiation and apoptosis. Mxi1, a Mad family member, was previously isolated in our laboratory on the basis of its early expression pattern in the territories of primary neurogenesis. In the first part of this thesis work, a functional characterization of Xmxi during Xenopus embryogenesis was performed. Consistent with an early role in neurogenesis, Xmxi1 was found to be positively regulated by the panneural genes, and proneural genes, as well as negatively by the Notch pathway. Loss-of-function experiments demonstrated an essential role for Xmxi1 in the establishment of a mature neural state that can be activated by factors that induce neuronal differentiation, such as SoxD and X ngnr-1. Overexpression of Xmxi1 resulted in a transient inhibition of neuronal differentiation, and at early tailbud stages both endogenous and ectopic neurogenesis were observed. While Xmxi1 enhances cell proliferation and apoptosis in the early Xenopus embryo, both activities appear not to be required for the function of Xmxi1 in primary neurogenesis. During primary neurogenesis, cell to cell signaling mediated by the Notch pathway restricts the number of cells that undergo neuronal differentiation. In the second part of this thesis work, an unbiased screen to identify early target genes of the Notch effector Enhancer-of-split related 1 (ESR1) was performed. A library enriched in early ESR1 target genes was prepared by PCR subtractive amplification using Xenopus ectodermal explants and a hormone-inducible antimorphic form of ESR1 (ESR1 VP16 GR). Through microarray analysis, 2,304 clones from the library enriched in ESR1 target genes, together with an additional 25,138 cDNA clones from two unrelated libraries 9, were screened for regualtion by ESR1 VP16-GR. In total, 55 genes were identified of these, 12 are members of the Notch pathway. In whole embryos, 43 of the 55 genes were strongly induced by ESR1 VP16 GR.de
dc.contributor.coRefereeKessel, Michael Prof. Dr.de
dc.subject.topicMolecular Biology & Neurosciences Programde
dc.subject.ger<i>Xenopus</i>de
dc.subject.gerNeurogenesede
dc.subject.ger<i>laevis</i>de
dc.subject.gerEntwicklungde
dc.subject.eng<i>Xenopus</i>de
dc.subject.engneurogenesisde
dc.subject.eng<i>laevis</i>de
dc.subject.engdevelopmentde
dc.subject.bk42.00de
dc.identifier.urnurn:nbn:de:gbv:7-webdoc-1006-2de
dc.identifier.purlwebdoc-1006de
dc.identifier.ppn527946613


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