Abstract
During development, precerebellar neurons migrate dorsoventrally from the rhombic lip to the floor plate. Some of these neurons cross the midline while others stop. We have identified a role for the slit receptor Rig-1/Robo3 in directing this process. During their tangential migration, neurons of all major hindbrain precerebellar nuclei express high levels of Rig-1 mRNA. Rig-1 expression is rapidly downregulated as their leading process crosses the floor plate. Interestingly, most precerebellar nuclei do not develop normally in Rig-1-deficient mice, as they fail to cross the midline. In addition, inferior olivary neurons, which normally send axons into the contralateral cerebellum, project ipsilaterally in Rig-1 mutant mice. Similarly, neurons of the lateral reticular nucleus and basilar pons are unable to migrate across the floor plate and instead remain ipsilateral. These results demonstrate that Rig-1 controls the ability of both precerebellar neuron cell bodies and their axons to cross the midline.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cerebellum / cytology
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Cerebellum / embryology*
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Cerebellum / metabolism
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Fetus
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Functional Laterality / genetics
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Gene Expression Regulation, Developmental / genetics
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Growth Cones / metabolism*
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Growth Cones / ultrastructure
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Mice
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Mice, Knockout
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Mutation / genetics
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / physiology*
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Neural Pathways / cytology
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Neural Pathways / embryology*
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Neural Pathways / metabolism
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Olivary Nucleus / cytology
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Olivary Nucleus / embryology
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Olivary Nucleus / metabolism
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Pons / cytology
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Pons / embryology
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Pons / metabolism
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RNA, Messenger / metabolism
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Receptors, Cell Surface
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Rhombencephalon / cytology
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Rhombencephalon / embryology*
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Rhombencephalon / metabolism
Substances
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Membrane Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Receptors, Cell Surface
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Robo3 protein, mouse
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Slit1 protein, mouse