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Status |
Public on Dec 29, 2010 |
Title |
Signaling to Transcription Networks in the Neuronal Retrograde Injury Response |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by array
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Summary |
Retrograde signaling from axon to soma activates intrinsic regeneration mechanisms in lesioned peripheral sensory neurons; however, the links between axonal injury signaling and the cell body response are not well understood. Here, we used phosphoproteomics and microarrays to implicate ~900 phosphoproteins in retrograde injury signaling in rat sciatic nerve axons in vivo and ~4500 transcripts in the in vivo response to injury in the dorsal root ganglia. Computational analyses of these data sets identified ~400 redundant axonal signaling networks connected to 39 transcription factors implicated in the sensory neuron response to axonal injury. Experimental perturbation of individual overrepresented signaling hub proteins, including Abl, AKT, p38, and protein kinase C, affected neurite outgrowth in sensory neurons. Paradoxically, however, combined perturbation of Abl together with other hub proteins had a reduced effect relative to perturbation of individual proteins. Our data indicate that nerve injury responses are controlled by multiple regulatory components, and suggest that network redundancies provide robustness to the injury response
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Overall design |
Microarrays were run on mRNA extracted from adult rat L4 and L5 DRGs cells after 1,3,8,12,16,18,24, and 28 hours after a sciatic nerve (proximal and distal) lesion.
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Contributor(s) |
Michaelevski I, Segal-Ruder Y, Rozenbaum M, Medzihradszky KF, Shalem O, Coppola G, Horn-Saban S, Ben-Yaakov K, Dagan SY, Rishal I, Geschwind DH, Pilpel Y, Burlingame AL, Fainzilber M |
Citation(s) |
20628157, 22246183 |
Submission date |
Dec 29, 2010 |
Last update date |
Aug 27, 2019 |
Contact name |
Giovanni Coppola |
E-mail(s) |
gcoppola@ucla.edu
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Phone |
310-794-4172
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Organization name |
UCLA
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Department |
Psychiatry and Neurology
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Lab |
Neurogenetics
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Street address |
1524 Gonda, 695 Charles Young Drive South
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City |
Los Angeles |
State/province |
CA |
ZIP/Postal code |
90095 |
Country |
USA |
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Platforms (1) |
GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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Samples (72)
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Relations |
BioProject |
PRJNA136731 |
Supplementary file |
Size |
Download |
File type/resource |
GSE26350_RAW.tar |
197.4 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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