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First published online 24 September 2003
doi: 10.1242/dev.00736
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1 Régionalisation Nerveuse CNRS/ENS UMR 8542, Ecole normale
supérieure, 46 rue d'Ulm, 75005 Paris, France
2 GSF-Research Centre, Institute of Mammalian Genetics, Ingolsträdter
Landstrasse 1, D-85764 Neuherberg and Max-Planck-Institute of Psychiatry,
Kraepelinstrasse 2-10, D-80809 Munich, Germany
Author for correspondence (e-mail:
wassef{at}wotan.ens.fr)
Accepted 21 July 2003
The cerebellum comprises a medial domain, called the vermis, flanked by two lateral subdivisions, the cerebellar hemispheres. Normal development of the vermis involves fusion of two lateral primordia on the dorsal midline. We investigated how the cerebellum fuses on the midline by combining a study of mid/hindbrain cell movements in avian embryos with the analysis of cerebellar fusion in normal and mutant mouse embryos. We found that, in avian embryos, divergent cell movements originating from a restricted medial domain located at the mid/hindbrain boundary produce the roof plate of the mid/hindbrain domain. Cells migrating anteriorly from this region populate the caudal midbrain roof plate whereas cells migrating posteriorly populate the cerebellar roof plate. In addition, the adjacent paramedial isthmic neuroepithelium also migrates caudalward and participates in the formation of the cerebellar midline region. We also found that the paramedial isthmic territory produces two distinct structures. First, the late developing velum medullaris that intervenes between the vermis and the midbrain, and second, a midline domain upon which the cerebellum fuses. Elimination or overgrowth of this isthmic domain in Wnt1sw/sw and En1+/Otx2lacZ mutant mice, respectively, impair cerebellar midline fusion. Because the isthmus-derived midline cerebellar domain displays a distinct expression pattern of genes involved in BMP signaling, we propose that the isthmus-derived cells provide both a substratum and signals that are essential for cerebellar fusion.
Key words: Cerebellum, Cerebellar midline fusion, Roof plate, Mid/hindbrain morphogenesis, Isthmus, Velum medullaris, Choroid plexus, Wnt1, Engrailed, Otx2, Swaying, Chick-quail chimera, Mouse
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