Neurodevelopment
The goals of this platform are to delineate molecular networks of brain development and to determine cellular functions of genes implicated in neurodevelopmental and degenerative disorders.
This platform focuses on the specification of neuronal identities and of neuronal connectivity by axon guidance molecules. Gene function studies are key to the research approach of this platform. Research on the specification of neuronal identity and connectivity centers around the meso-diencephalic dopamine system. This a heterogeneous set of dopamine neurons involved in coordination of movement as well as in motivation- and reward-related behaviors. These dopaminergic neurons exert differentiated functions due to molecular and cellular specializations and due to specificity in connectivity with forebrain structures. Genes belonging to dopaminergic transcription factors and their downstream targets and to axon guidance molecules and their signal transduction cascades are studied in the context of dopaminergic development and from viewpoints of generic mechanisms and application in regenerative medicine. Novel genes and mechanisms of development are explored in relation to neurological and psychiatric disorders, particularly epilepsy and autism in collaboration with the clinical and genetic departments. Genetics is being used to pinpoint genes causing aberrations in the developing and mature neocortex, and animal models are derived from the results.
Headlines of research are:
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downstream targets of transcription factors in the specification of dopamine neurons
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origin and heterogeneity of dopamine neurons
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axon guidance molecules in the establishment of differentiated wiring of dopaminergic systems
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receptor-ligand interactions and signal transduction of axon guidance molecules
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developmental gene networks in autism
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genes and transmitter systems in the development of epilepsy
Principle investigators: Burbach, De Graan, Pasterkamp
