DFG-Projekt: Isolierung und funktionelle Charakterisierung von nicht-kodierenden RNAs in der FOXG1-abhängigen Vorderhirnentwicklung und im Rett-Syndrom
Description of the project:
Determination and functional characterisation of non-coding RNAs in FOXG1-dependent forebrain development and Rett-syndrome
Rett-syndrome is an autism-spectrum disorder. Impaired neurodevelopment leads e.g. to progressive loss of cognitive capabilities, spastic paralysis, ataxia and epilepsy. 90% of Rett-syndrome cases are ascribed to mutations of MECP2, but FOXG1 haploinsufficiency results in similar phenotypes. Whether MECP2- and FOXG1-mediated Rett-syndrome share similarities on a molecular level has so far not been described in detail. Recent data suggest that expression of non-coding RNAs (ncRNA) is under control of MECP2 as well as FOXG1 and that they are implicated in the disease. Within this project we aim to perform a systematical analysis of molecular parallels between loss of MECP2 and FOXG1 in the forebrain of mice focussing on long ncRNAs (lncRNA). We will generate MECP2- and FOXG1-deficiency in FOXG1 expressing cells and elucidate transcriptomes in development and adulthood using high throughput sequencing. Further state-of-the-art interdisciplinary approaches within the fields of bioinformatics, molecular biology, and biochemistry will be used to predict and validate targets as well as molecular mechanisms on transcriptional and post-transcriptional level. With different approaches we will analyse the biogenesis of lncRNAs and their interaction with proteins, as well as with RNA and/or DNA. To reveal functional roles of specific lncRNA during neurodevelopment we will alter their expression and study the effects on proliferation, survival and neural specification of stem cells, as well as proper neuronal differentiation, as these processes are disturbed in Rett-syndrome. Using both Rett-syndrome mouse models we will elucidate whether and which specific lncRNA expression and mechanism is involved in the origin of this disease.
contact person: Prof. Dr. Rolf Backofen
Phone: +49 (0)761 203 7461
Email: backofen@informatik.uni-freiburg.de
Runtime:
Start of project: 01.01.2015
End of project: 31.10.2020
Project Management:
Albert-Ludwigs-University Freiburg
Prof. Dr. Rolf Backofen
Actual Research Report
Financing:
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