Peripheral nervous system genes expressed in central neurons induce growth on inhibitory substrates.
Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS's enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons.
Miami Project to Cure Paralysis, Department of Pharmacology, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
William J
WJ
Buchser
Robin P
RP
Smith
Jose R
JR
Pardinas
Candace L
CL
Haddox
Thomas
T
Hutson
Lawrence
L
Moon
Stanley R
SR
Hoffman
John L
JL
Bixby
Vance P
VP
Lemmon
D002531:Cerebellum / Q000166:cytology; D011508:Chondroitin Sulfate Proteoglycans; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007797:Laminin; D046228:Microarray Analysis; D009416:Nerve Regeneration / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D017933:Peripheral Nervous System / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics
D011508:Chondroitin Sulfate Proteoglycans; D018076:DNA, Complementary; D007797:Laminin; D009419:Nerve Tissue Proteins