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Role of Smad-interacting Protein 1 (Sip1/Zfhx1b) in the development of the cerebral cortex

dc.contributor.advisorTarabykin, Victor Prof. Dr.de
dc.contributor.authorMiquelajauregui, Amayade
dc.date.accessioned2006-05-19T06:55:19Zde
dc.date.accessioned2013-01-18T14:28:34Zde
dc.date.available2013-01-30T23:51:09Zde
dc.date.issued2006-05-19de
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-0006-B5EC-Cde
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-3294
dc.format.mimetypeapplication/pdfde
dc.language.isoengde
dc.rights.urihttp://webdoc.sub.gwdg.de/diss/copyr_diss.htmlde
dc.titleRole of Smad-interacting Protein 1 (Sip1/Zfhx1b) in the development of the cerebral cortexde
dc.typedoctoralThesisde
dc.contributor.refereeStühmer, Walter Prof. Dr.de
dc.date.examination2006-04-26de
dc.subject.dnb570 Biowissenschaftende
dc.subject.dnbBiologiede
dc.description.abstractengSmad-interacting protein 1 (Sip1/Zfhx1b) is a transcription factor that has been previously implicated in TGF-β/BMP signaling and in the etiology of the Mowat-Wilson syndrome. The expression of Sip1 was documented during mouse corticogenesis. The cortex-specific ablation of Sip1 resulted in the lack of hippocampus and dentate gyrus and in severe cortical lamination defects. Sip1 mutant mice exhibited cell death of differentiating cells and decreased proliferation in the region of the prospective hippocampus and dentate gyrus. In Sip1 mutants, the expression of the Wnt antagonist Sfrp1 was ectopically activated in the developing hippocampus and strongly up-regulated in post-mitotic cortical areas. The activity of the non-canonical Wnt effector, JNK, was inhibited in the prospective hippocampus of Sip1 mutants. The dentate gyrus defect was partially rescued by introducing in the Sip1-/- background, a stabilized form of the canonical Wnt mediator β-catenin. Sip1 is therefore essential to the development of the hippocampus and dentate gyrus, and regulates both canonical and non-canonical Wnt signaling via modulating the levels of Sfrp1. In the Sip1 mutant neocortex, upper layers were expanded at the expense of the deeper layers. The cell specification defects were accompanied by ectopic proliferation, increased apoptotic cell death and premature gliogenesis. As Sfrp1 was strongly up-regulated in the mutant neocortical areas, a role of Sip1 in the modulation of Wnt signaling in the neocortex is suggested.de
dc.contributor.coRefereeJäckle, Herbert Prof. Dr.de
dc.contributor.thirdRefereeBrose, Nils Prof. Dr.de
dc.subject.topicMolecular Biology & Neurosciences Programde
dc.subject.engBrainde
dc.subject.engHippocampusde
dc.subject.engDevelopmentde
dc.subject.engSmadde
dc.subject.engWntde
dc.subject.engTransgenicde
dc.subject.engMousede
dc.subject.bk42.13de
dc.subject.bk42.23de
dc.identifier.urnurn:nbn:de:gbv:7-webdoc-725-2de
dc.identifier.purlwebdoc-725de
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullWF 000: Molekularbiologiede
dc.subject.gokfullGentechnologiede
dc.subject.gokfullWK 000: Entwicklungsbiologiede
dc.identifier.ppn612119882de


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