{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:36:01Z","timestamp":1793162161466,"version":"4.5.0"},"reference-count":55,"publisher":"Society for Neuroscience","issue":"40","license":[{"start":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T00:00:00Z","timestamp":1522800000000},"content-version":"vor","delay-in-days":212,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2017,10,4]]},"abstract":"<jats:p>Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Kr\u00fcppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes. We identified a novel binding partner, MAPK10\/JNK3 kinase, and found that JNK3 (c-Jun N-terminal kinase 3) is critical for KLF9's axon-growth-suppressive activity. Interfering with a JNK3-binding domain or mutating two newly discovered serine phosphorylation acceptor sites, Ser106 and Ser110, effectively abolished KLF9's neurite growth suppression<jats:italic>in vitro<\/jats:italic>and promoted axon regeneration<jats:italic>in vivo<\/jats:italic>. These findings demonstrate a novel, physiologic role for the interaction of KLF9 and JNK3 in regenerative failure in the optic nerve and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>Injured CNS nerves fail to regenerate spontaneously. Promoting intrinsic axon growth capacity has been a major challenge in the field. Here, we demonstrate that knocking down Kr\u00fcppel-like transcription factor 9 (KLF9) via shRNA promotes long-distance axon regeneration after optic nerve injury and uncover a novel and important KLF9\u2013JNK3 interaction that contributes to axon growth suppression<jats:italic>in vitro<\/jats:italic>and regenerative failure<jats:italic>in vivo<\/jats:italic>. These studies suggest potential therapeutic approaches to promote axon regeneration in injury and other degenerative diseases in the adult CNS.<\/jats:p>","DOI":"10.1523\/jneurosci.0643-16.2017","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T00:40:25Z","timestamp":1504572025000},"page":"9632-9644","source":"Crossref","is-referenced-by-count":114,"title":["KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult 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