Novel regulatory mechanisms for the SoxC transcriptional network required for visual pathway development

Kun Che Chang, Jonathan Hertz, Xiong Zhang, Xiao Lu Jin, Peter Shaw, Brooke A. Derosa, Janet Y. Li, Praseeda Venugopalan, Daniel A. Valenzuela, Roshni D. Patel, Kristina R. Russano, Shomoukh A. Alshamekh, Catalina Sun, Kevin Tenerelli, Chenyi Li, Dmitri Velmeshev, Yuyan Cheng, Timothy M. Boyce, Alexandra Dreyfuss, Mohammed S. UddinKenneth J Muller, Derek M Dykxhoorn, Jeffrey L. Goldberg

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGCs. These data place Sox4 downstream of RE1 silencing transcription factor in regulating RGC fate, and further describe a newly identified, Sox4-regulated site for post-translational modification with small ubiquitin-related modifier (SUMOylation) in Sox11, which suppresses Sox11‘s nuclear localization and its ability to promote RGC differentiation, providing a mechanism for the SoxC familial compensation observed here and elsewhere in the nervous system. These data define novel regulatory mechanisms for this SoxC molecular network, and suggest pro-RGC molecular approaches for cell replacement-based therapies for glaucoma and other optic neuropathies.

Original languageEnglish (US)
Pages (from-to)4967-4981
Number of pages15
JournalJournal of Neuroscience
Volume37
Issue number19
DOIs
StatePublished - May 10 2017

Keywords

  • RGC
  • SoxC
  • Stem cell

ASJC Scopus subject areas

  • Neuroscience(all)

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    Chang, K. C., Hertz, J., Zhang, X., Jin, X. L., Shaw, P., Derosa, B. A., Li, J. Y., Venugopalan, P., Valenzuela, D. A., Patel, R. D., Russano, K. R., Alshamekh, S. A., Sun, C., Tenerelli, K., Li, C., Velmeshev, D., Cheng, Y., Boyce, T. M., Dreyfuss, A., ... Goldberg, J. L. (2017). Novel regulatory mechanisms for the SoxC transcriptional network required for visual pathway development. Journal of Neuroscience, 37(19), 4967-4981. https://doi.org/10.1523/JNEUROSCI.3430-13.2017