The functions of Smad1/5 in the Development and Survival of Midbrain Dopaminergic Neurons

Project Details


Nerve cells producing the neurotransmitter dopamine play a critical role in modulating essential brain functions such as thinking, emotions and motor control. Moreover, these cells are of particular medical relevance since their degeneration causes Parkinson’s disease. This neurological disease affects over 6 million individuals worldwide and is mostly characterized by progressive motor impairments with currently no cure. Previously considered as relatively independent processes, development, survival and degeneration of dopaminergic neurons are now increasingly regarded as tightly intertwined. However, very little is known about the pathways connecting and orchestrating these processes.

The overall aim of this proposal is to test the hypothesis that the two proteins Smad1 and Smad5, which are essential components of the bone morphogenetic protein (BMP) signaling pathway play a central role in development, survival and degeneration of dopaminergic neurons. We will use mouse mutagenesis combined with human stem cells and human midbrain organoids to test our hypothesis.

Our results are expected to considerably advance our understanding of the molecular underpinnings of the development and adult survival of dopaminergic neurons. Moreover, we expect to identify the Bmp/Smad pathway as a new potential drug target for Parkinson’s disease and advance the rational design of protocols used for the differentiation of stem cells to dopaminergic neurons currently developed for Parkinson’s disease cell replacement therapy.

Effective start/end date1/01/19 → …


  • United States-Israel Binational Science Foundation (BSF)


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