• Michael W Norsworthy, Fengfeng Bei, Riki Kawaguchi, Qing Wang, Nicholas M Tran, Yi Li, Benedikt Brommer, Yiming Zhang, Chen Wang, Joshua R Sanes, Giovanni Coppola, and Zhigang He.
• F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; PhD Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
• Neuron. 2017 Jun 21; 94 (6): 1112-1120.e4.

AbstractAt least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration. Transcriptome profiling indicated that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, α-RGCs, which preferentially regenerate following treatments such as Pten deletion, were killed by Sox11 overexpression. Thus, Sox11 promotes regeneration of non-α-RGCs, which are refractory to Pten deletion-induced regeneration. We conclude that Sox11 can reprogram adult RGCs to a growth-competent state, suggesting that different growth-promoting interventions promote regeneration in distinct neuronal types.Copyright © 2017 Elsevier Inc. All rights reserved.

34 keywords...

hide…