A Mouse Serine/Threonine Kinase Homologous to C. elegans UNC51 Functions in Parallel Fiber Formation of Cerebellar Granule Neurons

The formation of the cerebellar circuitry depends on the outgrowth of connections between the two principal classes of neurons, granule neurons and Purkinje neurons. To identify genes that function in axon outgrowth, we have isolated a mouse homolog of C. elegans UNC51, which is required for axon fo...

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Veröffentlicht in:Neuron (Cambridge, Mass.) Mass.), 1999-12, Vol.24 (4), p.833-846
Hauptverfasser: Tomoda, Toshifumi, Bhatt, Rupal S, Kuroyanagi, Hidehito, Shirasawa, Takuji, Hatten, Mary E
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container_title Neuron (Cambridge, Mass.)
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creator Tomoda, Toshifumi
Bhatt, Rupal S
Kuroyanagi, Hidehito
Shirasawa, Takuji
Hatten, Mary E
description The formation of the cerebellar circuitry depends on the outgrowth of connections between the two principal classes of neurons, granule neurons and Purkinje neurons. To identify genes that function in axon outgrowth, we have isolated a mouse homolog of C. elegans UNC51, which is required for axon formation, and tested its function in cerebellar granule neurons. Murine Unc51.1 encodes a novel serine/threonine kinase and is expressed in granule cells in the cerebellar cortex. Retroviral infection of immature granule cells with a dominant negative Unc51.1 results in inhibition of neurite outgrowth in vitro and in vivo. Moreover, infected neurons fail to express TAG-1 or neuron-specific β-tubulin, suggesting that development is arrested prior to this initial step of differentiation. Thus, Unc51.1 signals the program of gene expression leading to the formation of granule cell axons.
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subjects Amino Acid Sequence
Animals
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins
Cell Differentiation - physiology
Cerebellum - cytology
Cerebellum - growth & development
Cytoplasmic Granules - physiology
Genetic Vectors
Immunohistochemistry
In Situ Hybridization
Mice
Molecular Sequence Data
Mutation
Nerve Fibers - physiology
Neural Pathways - cytology
Neural Pathways - growth & development
Neural Pathways - physiology
Neurites - physiology
Neurons - physiology
Phenotype
Phylogeny
Plasmids - genetics
Protein-Serine-Threonine Kinases - physiology
Retroviridae - genetics
Reverse Transcriptase Polymerase Chain Reaction
Unc-51.1 protein
title A Mouse Serine/Threonine Kinase Homologous to C. elegans UNC51 Functions in Parallel Fiber Formation of Cerebellar Granule Neurons
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