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RESEARCH PRODUCT

Stably BDNF-GFP expressing embryonic stem cells exhibit a BDNF release-dependent enhancement of neuronal differentiation

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Brain-derived neurotrophic factor (BDNF) is known to be a crucial regulator of neuronal survival and synaptic plasticity in the mammalian brain. Furthermore, BDNF positively influences differentiation of embryonic neural precursors as well as of neural stem cells from adult neurogenic niches. To study the impact of cell-released BDNF on neural differentiation of embryonic stem cells (ESCs), which represent an attractive source for cell transplantation studies, we have generated BDNF-GFP overexpressing mouse ESC clones by knock-in technology. After neural differentiation in vitro, we observed that BDNF-GFP overexpressing ESC clones gave rise to an increased number of neurons as compared to control ESCs. Neurons derived from BDNF-GFP expressing ESCs harbored a more complex dendritic morphology and differentiated to a higher extent into the GABAergic lineage than controls. Moreover, we show that ESC-derived neurons released BDNF-GFP in an activity-dependent manner and displayed similar electrophysiological properties as cortical neurons. Thus, our study describes the generation of stably BDNF-GFP overexpressing ESCs which are ideally suited to investigate the ameliorating effects of BDNF in cell transplantation studies for various neuropathological conditions.