title: cJun promotes CNS axon growth.
abstract: A number of genes regulate regeneration of peripheral axons, but their ability to drive axon growth and regeneration in the central nervous system (CNS) remains largely untested. To address this question we overexpressed eight transcription factors and one small GTPase alone and in pairwise combinations to test whether combinatorial overexpression would have a synergistic impact on CNS neuron neurite growth. The Jun oncogene/signal transducer and activator of transcription 6 (JUN/STAT6) combination increased neurite growth in dissociated cortical neurons and in injured cortical slices. In injured cortical slices, JUN overexpression increased axon growth to a similar extent as JUN and STAT6 together. Interestingly, JUN overexpression was not associated with increased growth associated protein 43 (GAP43) or integrin alpha 7 (ITGA7) expression, though these are predicted transcriptional targets. This study demonstrates that JUN overexpression in cortical neurons stimulates axon growth, but does so independently of changes in expression of genes thought to be critical for JUNs effects on axon growth. We conclude that JUN activity underlies this CNS axonal growth response, and that it is mechanistically distinct from peripheral regeneration responses, in which increases in JUN expression coincide with increases in GAP43 expression.
authors: Department of Neuroscience, Center for Brain and Spinal Cord Repair, The Ohio State University Wexner Medical Center, 460 W 12th Ave, Columbus, OH 43210, USA; 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; University of Miami, Miami, FL, 33136, USA.
authors: Jessica K
authors: JK
authors: Lerch
authors: 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.
authors: Yania R
authors: YR
authors: Martínez-Ondaro
authors: 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; Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, 1400 NW 12th Ave, Miami, FL 33136, USA. Electronic address: jbixby@med.miami.edu.
authors: John L
authors: JL
authors: Bixby
authors: 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. Electronic address: vlemmon@med.miami.edu.
authors: Vance P
authors: VP
authors: Lemmon
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration; D055495:Neurogenesis; D016759:Oncogene Protein p65(gag-jun) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D019922:GAP-43 Protein; D039001:Integrin alpha Chains; D016759:Oncogene Protein p65(gag-jun); D050800:STAT6 Transcription Factor; C085725:integrin alpha7
keywords: Axon; Cortical neuron; Regeneration; Transcription factor; cJun