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Published November 27, 2001 | Supplemental Material
Journal Article Open

Direct imaging of in vivo neuronal migration in the developing cerebellum

Abstract

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 cerebellum [1]. It was thought to give rise to dorsally migrating granule cell precursors [2](Figure 1e); however, recent fate mapping studies have questioned the exclusive contributions of the URL to granule cells 3, 4 and 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 generated within the upper rhombic lip directly. Combining a novel GFP labeling strategy with in vivo time-lapse imaging, we find, contrary to the former view, that most URL-descendants migrate anterior toward the midhindbrain boundary (MHB) and then course ventrally along the MHB (Figure 1f). As the migrating neuronal precursors reach the MHB, they form ventrally extending projections, 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 recent fate maps. In addition, our results strongly suggest that the MHB plays a crucial role, not only in induction and patterning of the cerebellar anlage, but also in organizing its later morphogenesis by influencing cell migration.

Additional Information

© 2001 Elsevier Science Ltd. Received 13 July 2001, Revised 10 September 2001, Accepted 9 October 2001, Available online 29 November 2001. We would liKe to thank Mario Wultimann for intense discussions and suggestions; Connie Cepko for sharing data prior to publication; and Masahiko Hibi for providing us with the zebrafish atona/1-cDNA. We are grateful to Helen McBride, Sarah Ahlgren, Martin Garcia-Castro, and Andrew Groves for critical reading of the manuscript as well as to Arjun Menon and Jon Neri for excellent animal care. This work was supported by grants from the Deutsche Forschungsgemeinschaft (R.W.K.), the Human frontier Science Program (R.W.K), the Beckman Institute, the National Institutes of Health (S.E.F.), and the National lnstttute of Mental Health (S.E.F.).

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