Context-Dependent Function of Reelin in Neuronal Migration and Axonal Guidance

• Applicant: Professor Dr. Eckart Förster
• Co-Applicant: Professor Avihu Klar, Ph.D.
• Subject Area: Developmental Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 65717809

The project is based on the hypothesis that Reelin regulates both cell migration and the development of axonal connectivity in the central nervous system in a context-dependent manner by modifying the cellular response to other guidance molecules. To elucidate context-dependent modes of Reelin action, different functions of Reelin in the developing cortex and the spinal cord will be compared. Preliminary data suggest that in the spinal cord Reelin converts Netrin mediated attraction to repulsion. We plan to study the role of Reelin in the formation of the ipsilateral projection of spinal interneurons by using molecular genetic tools for gain- and loss of function studies for Reelin and components of the Reelin signaling cascade in chick embryos and tissue cultures of relevant mouse strains (wildtype, Reeler, VLDLR-/-, ApoER2-/-, Dab1-/-). We plan to characterize the Reelin downstream signaling that converts Netrin attraction to repulsion. For the developing neocortex and hippocampus, preliminary data suggest that soluble Reelin influences growth and branching of processes in a different mode when compared to substrate bound Reelin. We plan to investigate the role of Reelin in axon growth, - orientation, and - branching in the hippocampus and want to test whether Reelin mediates the positioning of neurons in the neocortex and hippocampus by modifying responsiveness to other guidance molecules. The project should contribute to a better understanding of some fundamental principles of cortical- and spinal cord development.

• DFG Programme: Research Grants
• International Connection: Israel