Transcriptomics

Dataset Information

12

Signaling to Transcription Networks in the Neuronal Retrograde Injury Response


ABSTRACT: 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 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.

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Keren Ben-Yaakov   Mike Fainzilber  Ida Rishal  Yael Segal-Ruder  Alma L Burlingame  Ophir Shalem  Izhak Michaelevski  Shirley Horn-Saban  Daniel H Geschwind  Giovanni Coppola  Katalin F Medzihradszky  Shachar Y Dagan  Yitzhak Pilpel  Meir Rozenbaum 

PROVIDER: E-GEOD-26350 | ArrayExpress | 2010-12-29

SECONDARY ACCESSION(S): GSE26350PRJNA136731

REPOSITORIES: GEO, ArrayExpress

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Publications


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 approximately 900 phosphoproteins in retrograde injury signaling in rat sciatic nerve axons in vivo and approximately 4500 transcripts in the in vivo response to injury in the dorsal root ganglia. Computational an  ...[more]

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