Transcriptomic Consequences of Neuregulin-1 Deficiency in Schizophrenia-Related Regions of the Mouse Brain

Scientists involved: Lukas Lachenmaier, Prof. Dr. Martin Bastmeyer, Dr. Franco Weth
Alumni: Philipp Kaiser

Failures of neurodevelopment are supposed to underlie severe mental disorders like schizophrenia. We therefore try to translate our expertise on brain development to the investigation of the pathogenic mechanisms of this disease. Schizophrenia is a devastating neurodevelopmental disorder, which manifests itself mostly during early adulthood. It is characterized by symptoms like delusions, hallucinations, emotional flattening and social withdrawal. Genetic factors contribute strongly to the pathogenesis of schizophrenia and neuregulin-1 is one of the well supported susceptibility genes. Its actual pathogenic mechanism, however, remains largely elusive. We therefore performed a detailed transcriptomic analysis using microarrays (Affymetrix) to elucidate the molecular consequences of neuregulin-1 hypomorphism in the mouse brain. To this end we used precision dissected tissue of disease-related brain regions at disease-related developmental stages. Subsequent to bioinformatic data mining,  candidate genes are validated by Digital Droplet PCR and fluorescent in situ hybridization for which we developed methods to allow for better linear quantification.  We are currently investigating the mechanistic role of a particularly promising candidate gene using protein biochemical and embryonic explant essays.
Collaboration partners: Prof. Dr. Carmen Birchmeier (Max-Delbrück-Zentrum, Berlin-Buch).