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 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 beta-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.
Tomoda
T
T
Laboratory of Developmental Neurobiology, The Rockefeller University, New York, New York 10021, USA.
Bhatt
R S
RS
Kuroyanagi
H
H
Shirasawa
T
T
Hatten
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002454:Cell Differentiation / Q000502:physiology; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development*; D003594:Cytoplasmic Granules / Q000502:physiology; D005822:Genetic Vectors; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009412:Nerve Fibers / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D029742:Caenorhabditis elegans Proteins; C112443:UNC-51 protein, C elegans; D017346:Protein Serine-Threonine Kinases