Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others

At 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 ad...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2017-06, Vol.94 (6), p.1112-1120.e4
Main Authors: Norsworthy, Michael W., Bei, Fengfeng, Kawaguchi, Riki, Wang, Qing, Tran, Nicholas M., Li, Yi, Brommer, Benedikt, Zhang, Yiming, Wang, Chen, Sanes, Joshua R., Coppola, Giovanni, He, Zhigang
Format: Article
Language:English
Subjects:
Animals
Axons - metabolism
Cell Survival
Cytoskeleton
Fibroblasts
Gene expression
Gene Expression Profiling
heterogeneity
Kinases
Mice
Microscopy, Fluorescence
Nerve Regeneration - genetics
Nervous system
Neuronal Outgrowth - genetics
Neurons
Optic nerve
Optic Nerve Injuries - metabolism
Optic Nerve Injuries - pathology
Phosphatase
Proteins
PTEN Phosphohydrolase - genetics
Regeneration
Regeneration - genetics
reprogramming
Retina
Retina - metabolism
Retina - pathology
Retinal ganglion cells
Retinal Ganglion Cells - cytology
Retinal Ganglion Cells - metabolism
Retinal Ganglion Cells - pathology
RGCs
Sox11
SOXC Transcription Factors - genetics
SOXC Transcription Factors - metabolism
Stem cells
Transcription factors
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Summary:At 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. •Sox11 promotes robust axon regeneration from injured adult RGCs•Sox11 re-activates a developmental axon growth program•Sox11 kills α-RGCs and promotes regeneration from other types•Pten deletion enhances axon regeneration induced by Sox11 expression Norsworthy et al. discovered that forced expression of Sox11, a transcription factor expressed in differentiating retinal progenitors, is able to reactivate an axon growth program and promote axon regeneration in subsets of adult RGCs but kills other types, suggesting that this and similar reprogramming strategies may be more complex than previously appreciated.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2017.05.035