The transcription factor ATF-3 promotes neurite outgrowth.
Dorsal root ganglion (DRG) neurons regenerate after a peripheral nerve injury but not after injury to their axons in the spinal cord. A key question is which transcription factors drive the changes in gene expression that increase the intrinsic growth state of peripherally injured sensory neurons? A prime candidate is activating transcription factor-3 (ATF-3), a transcription factor that we find is induced in all DRG neurons after peripheral, but not central axonal injury. Moreover, we show in adult DRG neurons that a preconditioning peripheral, but not central axonal injury, increases their growth, correlating closely with the pattern of ATF-3 induction. Using viral vectors, we delivered ATF-3 to cultured adult DRG neurons and find that ATF-3 enhances neurite outgrowth. Furthermore, ATF-3 promotes long sparsely branched neurites. ATF-3 overexpression did not increase c-Jun expression. ATF-3 may contribute, therefore, to neurite outgrowth by orchestrating the gene expression responses in injured neurons.
Seijffers
Rhona
R
Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Allchorne
Andrew J
AJ
Woolf
Clifford J
CJ
D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000293:injuries / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D005822:Genetic Vectors / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000235:genetics*; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000166:cytology / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019051:Rhizotomy / Q000009:adverse effects; D013126:Spinal Nerve Roots / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D016755:Proto-Oncogene Proteins c-jun