Objective The cerebellum coordinates the body’s movements. It consists of distinct layers of neuronal populations, but during embryonic development, these neurons are generated distantly from their final locations. In zebrafish, this means that cerebellar neurons have to migrate from the upper rhombic lip to the midbrain-hindbrain boundary and further. While descriptions of the migratory pathways for the different neuronal populations have become available in recent years, fundamental questions of this process are still unanswered. Firstly, we currently do not know how guidance of these cells is achieved and translated into directional motility. Activity could be a guiding cue, as it creates intracellular Ca2+-transients which determine directionality in cerebellar neurons. Similarly, depletion of Cadherin-2, a cell-adhesion molecule and key regulator of cell migration, leads to loss of directionality. If activity works through Cadherin-2 to guide cells, it would present a novel way of transmitting information from outside to the inside of cells. We will test this notion using the latest genetic tools. Secondly, Cadherin-2 influences centrosome-positioning, yet we do not know the molecular mechanism of this. IQGAP1 could be the link between Caherin-2 and the microtubules, but this remains to be proven. Thirdly, in order to generate movement of the cells, the forces from the cytoskeleton need to be transmitted to the nucleus. Two models for such mechanisms are being debated, and we will test both in migrating cells in vivo. To address these questions, we will use an interdisciplinary approach combining techniques and knowledge from cell biology, developmental biology and genetics with advanced in vivo time-lapse imaging.Understanding how the cells’ migration is guided and regulated will improve the fundamental knowledge for the development of therapies for patients suffering from brain injuries or lissencephalies, and create a unique focus of cerebellar research in Europe. Fields of science natural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencescell biologynatural sciencesbiological sciencesdevelopmental biology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2013-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator TECHNISCHE UNIVERSITAET BRAUNSCHWEIG EU contribution € 161 968,80 Address UNIVERSITAETSPLATZ 2 38106 Braunschweig Germany See on map Region Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Reinhard Köster (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data