In vivo analysis of cell biological and molecular mechanisms of nucleokinetic cell migration during development of the cerebellum

• Applicant: Professor Dr. Reinhard W. Köster
• Subject Area: Developmental Neurobiology
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 48923063

Nucleokinesis, the active forward translocation of the nucleus organized by the centrosome and the microtubule skeleton, is essential for proper neuronal migration. We aim to resolve the cell biological coordination of nucleokinetic migration and the underlying molecular mechanisms in neuronal precursors of the almost transparent zebrafish cerebellum. Using high resolution in vivo time-lapse microscopy, we will characterize the coordination of the centrosome, the microtubuli and the nucleus during different stages of migration in cerebellar neuronal precursors undergoing nucleokinesis. Through interference with the function of Lis1, Nde, Ndel and aPKC􀀁 the molecular mechanisms will be addressed that govern nucleokinesis. Furthermore, analysis of neuronal migration in the cerebellum of the zebrafish mutants nagie oko (nok) and heart and soul (has) is aimed at elucidating novel factors involved in the coordination of nucleokinetic neuronal migration. Lissencephaly the most common disease in humans resulting from defective neuronal migration is caused by the failure of neuronal precursors to properly undergo nucleokinesis. Thus, we finally aim to establish a lissencephaly disease model accessible for in vivo imaging approaches to record the onset and progression of this disease within the cerebellum. This model together with the obtained cell biological and molecular data will significantly contribute to the understanding of the aetiology of neuronal migration disorders.

• DFG Programme: Research Grants