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J Neurosci 2010 Nov 17;3046:15464-78. doi: 10.1523/JNEUROSCI.1800-10.2010.
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Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs.

Zivraj KH , Tung YC , Piper M , Gumy L , Fawcett JW , Yeo GS , Holt CE .

Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons, yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones. Here laser capture microdissection (LCM) was used to isolate the growth cones of retinal ganglion cell (RGC) axons of two vertebrate species, mouse and Xenopus, coupled with unbiased genomewide microarray profiling. An unexpectedly large pool of mRNAs defined predominant pathways in protein synthesis, oxidative phosphorylation, cancer, neurological disease, and signaling. Comparative profiling of "young" (pathfinding) versus "old" (target-arriving) Xenopus growth cones revealed that the number and complexity of transcripts increases dramatically with age. Many presynaptic protein mRNAs are present exclusively in old growth cones, suggesting that functionally related sets of mRNAs are targeted to growth cones in a developmentally regulated way. Remarkably, a subset of mRNAs was significantly enriched in the growth cone compared with the axon compartment, indicating that mechanisms exist to localize mRNAs selectively to the growth cone. Furthermore, some receptor transcripts (e.g., EphB4), present exclusively in old growth cones, were equally abundant in young and old cell bodies, indicating that RNA trafficking from the soma is developmentally regulated. Our findings show that the mRNA repertoire in growth cones is regulated dynamically with age and suggest that mRNA localization is tailored to match the functional demands of the growing axon tip as it transforms into the presynaptic terminal.

PubMed ID: 21084603
PMC ID: PMC3683943
Article link: J Neurosci
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actr2 arpc1a coro1a coro1c efna3 efnb2 eif5a ephb4 fgf1 fgfr2 fscn1 fth1.1 h3-5 kif1a pfn2 ppia ppp1r9a prph rhoa rps13 rpsa septin5 sf3a2 slc25a5 slc7a5 sntb2 tmsb4x tuba1c tuba1cl ubc vps4b
Antibodies: FM1-43

GEO Series: GSE25166: NCBI

Article Images: [+] show captions
References [+] :
Andreassi, An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons. 2010, Pubmed