Role for Reelin in adult neurogenesis of the dentate gyrus

• Applicant: Dr. Bianka Brunne, since 7/2017
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213820067

Reelin has been known for many years as a glycoprotein controlling layer formation in the brain during embryonic development. Reelin expression is decreased in a variety of neuropsychiatric disorders suggesting additional functions in the adult. Here we will test the hypothesis that Reelin plays a role in stabilizing adult brain architecture. This new hypothesis is based on two unexpected findings: First, we have shown that malfunction of Reelin in the adult results in neuronal repositioning and loss of laminated organization. Second, we have shown that Reelin signalling indeed stabilizes the actin cytoskeleton of neurons by phosphorylating cofilin. We aim to study how experimentally induced malfunction of Reelin in the adult induces structural reorganization. How do differentiated neurons change their positions? We will monitor adult, GFP-labeled neurons using real-time microscopy. We will study our conditional Reelin mutant for effects of Reelin deficiency induced in adult age on the behaviour of the animals and on the physiological characteristics of repositioned and probably reconnected neurons. We will use high-pressure freezing of unfixed tissue and immunogold labeling to document sites of Reelin signaling in the adult brain. We expect important insights into novel functions of an old and well-known developmental molecule.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Michael Frotscher, until 7/2017 (†)