Direct imaging of in vivo neuronal migration in the developing cerebellum

The upper rhombic lip (URL), a germinal zone in the dorsoanterior hindbrain , has long been known to be a source for neurons of the vertebrate cerebell um [1]. It was thought to give rise to dorsally migrating granule cell prec ursors [2] (Figure le); however, recent fate mapping studies have questione d the exclusive contributions of the URL to granule cells [3-5]. By taking advantage of the clarity of the zebrafish embryo during the stages of brain morphogenesis, we have followed the fate of neuronal precursor cells gener ated within the upper rhombic lip directly. Combining a novel GFP labeling strategy with in vivo time-lapse imaging, we find, contrary to the former v iew, that most URL-descendants migrate anterior toward the midhindbrain bou ndary (MHB) and then course ventrally along the MHB (Figure 1f). As the mig rating neuronal precursors reach the MHB, they form ventrally extending pro jections, likely axons, and continue ventral migration to settle outside of the cerebellum, in the region of the ventral brainstem. Thus, we define a new pathway for URL-derived neuronal precursor cells consistent with the re cent fate maps. In addition, our results strongly suggest that the MHB play s a crucial role, not only in induction and patterning of the cerebellar an lage, but also in organizing its later morphogenesis by influencing cell mi gration.