During my diploma thesis I focused on the expression of Notch signaling receptors and ligands in the human placenta and the role of the active Notch pathway in placental cell lines and primary cultures. Notch signaling is a highly conserved pathway that, dependent on the cellular context, can promote or suppress cell proliferation, cell death, acquisition of specific cell fates or activation of differentiation programs. Since gene chip analyses has revealed that several members of the Notch

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... way are widely expressed in the human placenta I analysed mRNA expression of the four Notch receptors and five ligands in human gestational tissues and cells using semi-quantitative RT-PCR. To confirm these results, I performed immunohistochemical analyses focussing on first trimester tissue. These data revealed that all receptors and ligands are expressed in first trimester placenta, some of them being restricted to a subset of placenta cell populations. In order to study the activitiy of the Notch cascade I transiently transfected a trophoblastic cell line with luciferase vectors containing wilde type and mutated CBF1 binding sites revealing an endogenous Notch activity in this cell line. Additionally, I could further induce Notch activity by overexpressing the Notch intracellular domain. Using a co-culture model with the trophoblastic cell line and isolated primary decidual fibroblast I could show that the Notch pathway can be elucidated by the fibroblast cell population. In all transfection studies, the g-secretase inhibitor DAPT was used to block the Notch pathway being a control for the endogenous and fibroblast-induced Notch activity. Finally, I could figure out that DAPT-induced blocking of the Notch pathway stimulates the migration not only of the trophoblastic cell line but also of villous explant culture-derived extravillous trophoblasts in a dose dependent manner. These data not only proved the presence of Notch receptors and ligands in the human placenta but also showed specific expression patterns suggesting [...]