Funding tool: Basic research projects
Project-ID: LS13-002
Project start: 01. März 2015
Project end: will follow
Runtime: 36 months / finished
Funding amount: € 245.000,00

Brief summary:

Genomic imprinting is an epigenetic regulatory mechanism that leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for embryonic development and regulates critical aspects of brain function and homeostasis. Deregulation of imprinting results in an imbalance of specific gene expression and causes many disease conditions including cancer, neurodevelopmental disorders and psychiatric diseases. The functional relevance of imprinting at the individual cell level is however poorly understood for most imprinted genes. It is therefore essential to address the fundamental question to which extent neuronal cell-type specific imprinting can play a role in the assembly and/or function of neuronal circuits and thus impact behavior. Up to date, the cell-type specificity of genomic imprinting in the brain remains however enigmatic due to a lack of appropriate assays. To overcome this limitation, we have recently advanced the unparalleled MADM (Mosaic Analysis with Double Markers) technology which offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level. Here we propose to apply the MADM system to 1) probe for the effects of genomic imprinting at the unprecedented single cell resolution and 2) to map the neuron-type specificity of genomic imprinting and its relevance for neuronal circuits in the brain. The obtained results are expected to provide fundamental insights into the role of genomic imprinting for brain development and function. In a broader context, the project is expected to significantly strengthen basic Neuroscience research in Lower Austria by advancing our understanding of the underlying pathogenic molecular-genetic basis of devastating neurodevelopmental disorders and psychiatric diseases in human. Thereby this project shall also contribute to a better overall healthcare in Lower Austria and for our society in general.

Keywords:
Neuronal Development, Single Cell Analysis, Genomic Imprinting, Mosaic Analysis with Double Markers (MADM)