Cerebellar granule cells undergo profound and rapid morphological modifications during development while they migrate from their birthplace at the surface of the cerebellar cortex to its deepest layer. Post-mitotic granule cells extend bipolar axons and sequentially use the two main modes of migration, tangential and radial, to reach their final destinations. Recent studies show that protein degradation involving key cell-cycle regulators controls granule cell axon extension. The use of knockout mice deficient in different axon-guidance molecules combined with cutting-edge imaging methods has started to shed light on the molecular mechanisms that trigger granule cell migration. These studies suggest that a major reorganization of the cytoskeleton occurs as granule cells switch from tangential to radial migration.
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