Notch1 signaling antagonizes transforming growth factor-β pathway and induces apoptosis in rabbit trophoblast stem cells.

During mammalian development, placental growth needs to be tightly controlled by apoptosis. However, despite the potentially significant problems, the strategies used to balance growth and apoptosis have remained elusive. Here we report that activation of the Notch1 signal pathway inhibits transduction of transforming growth factor (TGF)-β signaling, which leads to cell cycle arrest and apoptosis in rabbit trophoblast stem cells (TSCs). The subcellular location of notch intracellular domain 1 (NICD1) appears to determine whether TGF-β signaling will be inhibited or not. Moreover, changes in NICD1 subcellular location are regulated by intracellular calcium distribution. Collectively, these results establish a potential mechanism whereby TSCs can balance growth and apoptosis, and thus guarantee the development of the fetus.