RGD Reference Report - A SnoN-Ccd1 pathway promotes axonal morphogenesis in the mammalian brain. - Rat Genome Database

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A SnoN-Ccd1 pathway promotes axonal morphogenesis in the mammalian brain.

Authors: Ikeuchi, Y  Stegmuller, J  Netherton, S  Huynh, MA  Masu, M  Frank, D  Bonni, S  Bonni, A 
Citation: Ikeuchi Y, etal., J Neurosci. 2009 Apr 1;29(13):4312-21.
RGD ID: 2308917
Pubmed: PMID:19339625   (View Abstract at PubMed)
PMCID: PMC2853192   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.0126-09.2009   (Journal Full-text)

The transcriptional corepressor SnoN is a critical regulator of axonal morphogenesis, but how SnoN drives axonal growth is unknown. Here, we report that gene-profiling analyses in cerebellar granule neurons reveal that the large majority of genes altered upon SnoN knockdown are surprisingly downregulated, suggesting that SnoN may activate transcription in neurons. Accordingly, we find that the transcriptional coactivator p300 interacts with SnoN, and p300 plays a critical role in SnoN-induced axon growth. We also identify the gene encoding the signaling scaffold protein Ccd1 as a critical target of SnoN in neurons. Ccd1 localizes to the actin cytoskeleton, is enriched at axon terminals in neurons, and activates the axon growth-promoting kinase JNK (c-Jun N-terminal protein kinase). Knockdown of Ccd1 in neurons reduces axonal length and suppresses the ability of SnoN to promote axonal growth. Importantly, Ccd1 knockdown in rat pups profoundly impairs the formation of granule neuron parallel fiber axons in the rat cerebellar cortex in vivo. These findings define a novel SnoN-Ccd1 link that promotes axonal growth in the mammalian brain, with important implications for axonal development and regeneration.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
axon terminus  IDA 2308917 RGD 
neuronal cell body  IDA 2308917 RGD 
protein-containing complex  IDA 2308917 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mitogen-activated protein kinase kinase kinase binding  IDA 2308917 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dixdc1  (DIX domain containing 1)
Ep300  (E1A binding protein p300)
Skil  (SKI-like proto-oncogene)

Objects referenced in this article
Gene Casp12 caspase 12 Rattus norvegicus

Additional Information