TY - JOUR
T1 - Transcriptional profiling of intrinsic PNS factors in the postnatal mouse
AU - Smith, Robin P.
AU - Lerch-Haner, Jessica K.
AU - Pardinas, Jose R.
AU - Buchser, William J.
AU - Bixby, John L.
AU - Lemmon, Vance P.
N1 - Funding Information:
This work was supported by the Miami Project to Cure Paralysis , the Buoniconti Fund , DOD W81XWH-05-1-0061 , grant no. 2396 from the Paralyzed Veterans of America Research Foundation and NIH HD057632 and NS059866 . W. Buchser is a recipient of a Lois Pope LIFE Scholar award. V. Lemmon holds the Walter G. Ross Distinguished Chair in Developmental Neuroscience at the University of Miami. The authors would like to thank Pieter J. Peeters for his generous gift of the raw LCM DRG microarray data files.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - Cerebellar granule neuron
KW - Dorsal root ganglion
KW - High content analysis
KW - STAT3
KW - Screen
KW - Systems biology
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=78650892989&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2010.07.015
DO - 10.1016/j.mcn.2010.07.015
M3 - Article
C2 - 20696251
AN - SCOPUS:78650892989
SN - 1044-7431
VL - 46
SP - 32
EP - 44
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 1
ER -