Transcriptional profiling of intrinsic PNS factors in the postnatal mouse.
Neurons in the peripheral nervous system (PNS) display a higher capacity to regenerate after injury than those in the central nervous system, suggesting cell specific transcriptional modules underlying axon growth and inhibition. We report a systems biology based search for PNS specific transcription factors (TFs). Messenger RNAs enriched in dorsal root ganglion (DRG) neurons compared to cerebellar granule neurons (CGNs) were identified using subtractive hybridization and DNA microarray approaches. Network and transcription factor binding site enrichment analyses were used to further identify TFs that may be differentially active. Combining these techniques, we identified 32 TFs likely to be enriched and/or active in the PNS. Twenty-five of these TFs were then tested for an ability to promote CNS neurite outgrowth in an overexpression screen. Real-time PCR and immunohistochemical studies confirmed that one representative TF, STAT3, is intrinsic to PNS neurons, and that constitutively active STAT3 is sufficient to promote CGN neurite outgrowth.
Smith
Robin P
RP
The Miami Project to Cure Paralysis, Department of Neurological Surgery, Miller School of Medicine, University of Miami, 1400 NW 12th Ave, Miami, FL 33136, USA.
Lerch-Haner
Jessica K
JK
Pardinas
Jose R
JR
Buchser
William J
WJ
Bixby
John L
JL
Lemmon
Vance P
VP
D000818:Animals; D002531:Cerebellum / Q000166:cytology; D005727:Ganglia, Spinal / Q000166:cytology; D020869:Gene Expression Profiling / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009693:Nucleic Acid Hybridization / Q000379:methods; D017933:Peripheral Nervous System / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D014157:Transcription Factors