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• W761588865 abstract "Transforming Growth Factor βs (TGF-βs) are multifunctional cytokines and mediate a wide range of biological activities in a context dependent manner. TGF-βs and their signalling effectors are expressed in the forebrain, but little is known upon their role during forebrain development. The aim of this study was to investigate possible functions of TGF-β in neuronal cells of the developing forebrain. As a model primary cortical and hippocampal cultures isolated from E14.5 and E16.5 mouse embryonic brains were used which were shown to be responsive for TGF-β signals. Exogenic treatment with TGF-β induced cell cycle exit of neural progenitors through regulation of cell cycle control genes and leads to a reduction of Nestin- and Pax6-positive progenitor cells. At the same time an increased expression of the neuronal markers HuC/D and NeuN could be observed, indicating enhanced neuronal differentiation. This TGF-β induced neurogenesis was dependent on the activation of Smad-proteins and on the developmental stage of the respective progenitors. While E14.5 derived progenitors did not respond with increased neurogenesis to the TGF-β stimulus, later-stage progenitors of E16.5 produced around 34% more neurons compared to unstimulated cultures. Furthermore in this study several downstream target genes of the TGF-β signalling pathway in primary hippocampal cultures isolated from E16.5 mouse embryos could be identified. These TGF-b regulated genes include molecules of the extracellular matrix like Ctgf, Timp3, TenascinC and the Integrins α 3 and α 5, as well as molecules which exert regulating functions on members of the TGF-β superfamiliy themselves like Smad7, Igf2r and Fstl3. By the regulation of genes involved in the mediation of Notch and Wnt signals a cross talk between TGF-β signalling pathways and the developmentally important Notch and Wnt signalling pathways could be discovered. Furthermore TGF-β influenced the expression of genes playing a role in neuronal differentiation like Gata2, Runx1, Id3 and Nedd9. Using siRNA-mediated knock-down of the TGF-β-induced target genes Ctgf, Gata2, Runx1 and Nedd9, Nedd9 could be identified as essential signalling component for TGF-β-dependent increase in neuronal differentiation. Expression of this scaffolding protein, that is mainly described as signalling molecule of the integrin pathway through focal adhesions, was not only induced after TGF-β treatment but was also associated with morphological changes of the Nestin-positive progenitor pool observed upon exposure to TGF-β. This morphological changes seems to represent the TGF-β mediated transition from one type of progenitor cells to another, more differentiated type. The results of this study show an implication for TGF-β during the differentiation of neural progenitors of the forebrain during later phases of their development. In This process TGF-β may transform the progenitor pool into a status that mediates neuronal differentiation after induction of the last mitotic division of neural progenitors." @default.
• W761588865 created "2016-06-24" @default.
• W761588865 creator A5000660237 @default.
• W761588865 date "2022-02-17" @default.
• W761588865 modified "2023-10-01" @default.
• W761588865 title "Untersuchungen zu Bedeutung von TGF-β während der Entwicklung des Vorderhirns" @default.
• W761588865 doi "https://doi.org/10.53846/goediss-322" @default.
• W761588865 hasPublicationYear "2022" @default.
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