FORNEUROCELL II

BAVARIAN RESEARCH ASSOCIATION FOR ADULT NEURONAL STEM CELLS

Canonical Wnt-signalling in dopaminergic differentiation in vivo and in vitro

Parkinson’s Disease (PD) is characterized by the progressive degeneration of dopamine (DA) -synthesizing neurons in the human ventral midbrain. Stem cell-based regenerative therapies for PD have not been implemented so far due to ethical and practical concerns. The recent discovery that adult human somatic cells can be reprogrammed to a stem cell-like state, so-called induced pluripotent stem (iPS) cells, and subsequently differentiated into all types of cells, including dopaminergic neurons, provides a completely new outlook on regenerative therapies for PD. The canonical Wnt1/ß-catenin signaling pathway plays a crucial role in the induction and differentiation of ventral midbrain dopaminergic neurons in the mouse embryo, but this secreted factor and its intracellular signaling pathway has not been recognized as a potentially very important component in the so far rather inefficient dopaminergic differentiation protocols. In this subproject, we aim at determining the role of the canonical Wnt/ß-catenin pathway in the differentiation of neural progenitor cells in vivo as well as of mouse and human iPS cells in vitro into midbrain dopaminergic neurons. Another step in developing an applicable regenerative therapy for PD might be taken in the case that activation of this signaling pathway turns out to be particularly beneficial for the differentiation of stem cells into dopaminergic neurons.