Abstract
At least 30 types of retinal ganglion cells (RGCs) senddistinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Herewe tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regenerationof other types. From a screen of transcription factors, we identified Sox11 as one that could inducesubstantial axon regeneration. Transcriptomeprofiling 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.
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