Abstract
The transmembrane semaphorin protein Sema6A is broadly expressed in the developing nervous system. Sema6A repels several classes of developing axons in vitro and contributes to thalamocortical axon guidance in vivo. Here we show that during cerebellum development, Sema6A is selectively expressed by postmitotic granule cells during their tangential migration in the deep external granule cell layer, but not during their radial migration. In Sema6A-deficient mice, many granule cells remain ectopic in the molecular layer where they differentiate and are contacted by mossy fibers. The analysis of ectopic granule cell morphology in Sema6a-/- mice, and of granule cell migration and neurite outgrowth in cerebellar explants, suggests that Sema6A controls the initiation of granule cell radial migration, probably through a modulation of nuclear and/or soma translocation. Finally, the analysis of mouse chimeras suggests that this function of Sema6A is primarily non-cell-autonomous.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Animals, Newborn
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Biotin / analogs & derivatives
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Biotin / metabolism
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Blotting, Western / methods
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Bromodeoxyuridine / metabolism
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Calcium-Binding Proteins / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Adhesion Molecules, Neuronal / metabolism
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Cell Differentiation / physiology
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Cell Movement / physiology*
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Cell Polarity / physiology
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Cell Proliferation
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Cells, Cultured
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Cerebellum / cytology*
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Contactin 2
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Cricetinae
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Cricetulus
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Dextrans / metabolism
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Glial Fibrillary Acidic Protein / metabolism
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Green Fluorescent Proteins / biosynthesis
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Immunohistochemistry / methods
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In Situ Hybridization / methods
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microscopy, Video / methods
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Neurons / physiology*
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Phalloidine / metabolism
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Semaphorins / deficiency
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Semaphorins / physiology*
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Time Factors
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Tubulin / metabolism
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Vesicular Glutamate Transport Protein 2 / metabolism
Substances
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Atoh1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Calcium-Binding Proteins
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Cell Adhesion Molecules, Neuronal
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Cntn2 protein, mouse
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Contactin 2
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Dextrans
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Glial Fibrillary Acidic Protein
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Sema6a protein, mouse
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Semaphorins
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Slc17a6 protein, mouse
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Tubulin
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Vesicular Glutamate Transport Protein 2
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biotinylated dextran amine
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Green Fluorescent Proteins
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Phalloidine
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Biotin
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases
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Camk4 protein, mouse
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Bromodeoxyuridine