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Neuron. 2017 Jun 21;94(6):1112-1120.e4. doi: 10.1016/j.neuron.2017.05.035.

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

Author information

1
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.
2
F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: fbei@bwh.harvard.edu.
3
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA 90095-1761, USA.
4
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
5
F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
6
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA 90095-1761, USA; Department of Neurology, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA 90095-1761, USA. Electronic address: gcoppola@ucla.edu.
7
F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: zhigang.he@childrens.harvard.edu.

Abstract

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.

KEYWORDS:

RGCs; Sox11; heterogeneity; optic nerve; regeneration; reprogramming

PMID:
28641110
PMCID:
PMC5519288
DOI:
10.1016/j.neuron.2017.05.035
[Indexed for MEDLINE]
Free PMC Article

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