RT Journal Article
SR Electronic
T1 A SnoN–Ccd1 Pathway Promotes Axonal Morphogenesis in the Mammalian Brain
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4312
OP 4321
DO 10.1523/JNEUROSCI.0126-09.2009
VO 29
IS 13
A1 Yoshiho Ikeuchi
A1 Judith Stegmüller
A1 Stuart Netherton
A1 Mai Anh Huynh
A1 Masayuki Masu
A1 David Frank
A1 Shirin Bonni
A1 Azad Bonni
YR 2009
UL http://www.jneurosci.org/content/29/13/4312.abstract
AB 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.