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Authors & Affiliations
Pascal Schneider, Tristan Leu, Joachim Fandrey
Abstract
Primary cilia, also called "the cells antenna", are centriole based sensory cellular organelles, which are present on almost all mammalian cells and became important during the last decades. They realize a variety of functions, including maintaining neuroplasticity and the adaption to hypoxic conditions via a variety of signalling pathways, including the SHH-signalling, the MEK-ERK-signalling or the PDGFRa-signalling pathway. Based on these observations, the work pursued the goal to investigate the interplay of the hypoxia-inducible factor 1alpha and primary cilia in neuronal cells. The establishment of primary neuronal HIF1alpha-knockout cells, based on a specific tamoxifen induced Cre/LoxP-system, and siRNA-mediated SH‑SY5Y HIF1alpha-knockdown cells served as the base for this work. Thereby the knockout and knockdown efficiencies were determined by quantitative PCR analysis and Western-Blotting. By using the cells, we investigate a connection between the transcription factor and the “cellular antenna” and define its interplay more precisely by focussing on a variety of signalling pathways and the primary cilia morphology. In particular, influences on the expression of the Notch signalling components Notch 3 and 4, as well as on GATA3 could be observed. The significance of the interaction of both factors, as well as the transferability to diseases associated with hypoxia, such as ischemic stroke, must be investigated by further experiments.