Regulating activity and expression of cell signaling molecules in nervous system development and disease

Abstract

The development of a fully functional brain requires the orchestration of simultaneously coordinated migration, projection and network formation to connect millions of neurons. When neuronal connections are lost or neurons die as a result of neurodegenerative disease or injury, the regenerative capacities of the adult central nervous system (CNS) are limited. In order to develop clinical strategies to improve this regenerative potential, we need to 1) increase our understanding of the guidance cues and cellular processes that regulate neural circuit formation during development, and 2) investigate the pathological changes that occur following adult CNS injury and/or disease. These insights will lead to novel therapeutic targets for future (pre)clinical studies. This thesis contributes to our understanding of; 1) signaling downstream of the axon guidance receptor Neogenin; 2) intrinsic and extrinsic regulation of neuronal migration; and 3) molecular changes associated with human epilepsy. These approaches not only identify novel factors involved in the regulation of neural development, but also characterize the pathology of a neurological disease.