cJun promotes CNS axon growth

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• 作者：Jessica K. Lerch^a ; ^b ; ^d ; Yania R. Martí ; nez-Ondaro^b ; John L. Bixby^b ; ^c ; ^{jbixby@med.miami.edu" class="auth_mail} ; Vance P. Lemmon^b ; ^{vlemmon@med.miami.edu" class="auth_mail}
• 关键词：JUN ; Jun oncogene ; GAP43 ; growth associated protein 43 ; ITGA7 ; integrin alpha 7 ; PN ; postnatal day ; SOCS3 ; suppressor of cytokine signaling 3 ; KLFs ; Krü ; ppel-like transcription factors ; PTEN ; phosphatase and tensin homologue ; DRG ; dorsal root ganglion ; CGNs ; cerebellar granular neurons ; TF ; transcription factor ; Oxr1 ; oxidase resistance 1 ; BHLHE40 ; basic helix-loop-helix family member e40
• 刊名：Molecular and Cellular Neuroscience
• 出版年：March 2014
• 年：2014
• 卷：59
• 期：Complete
• 页码：97-105
• 全文大小：1581 K

文摘

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.