June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Novel transcriptional mechanisms regulate visual pathway development
Author Affiliations & Notes
  • Kevin Tenerelli
    Shiley Eye Center, University of California, San Diego, La Jolla, CA
  • Xiong Zhang
    Shiley Eye Center, University of California, San Diego, La Jolla, CA
  • Jonathan Hertz
    Neuroscience Graduate Program, University of Miami, Miami, FL
  • Praseeda Venugopalan
    Shiley Eye Center, University of California, San Diego, La Jolla, CA
  • Catalina B. Sun
    Shiley Eye Center, University of California, San Diego, La Jolla, CA
  • Shomoukh A. Alshamekh
    Ophthalmology, University of Miami, Miami, FL
  • Jeffrey L Goldberg
    Shiley Eye Center, University of California, San Diego, La Jolla, CA
  • Footnotes
    Commercial Relationships Kevin Tenerelli, None; Xiong Zhang, None; Jonathan Hertz, None; Praseeda Venugopalan, None; Catalina Sun, None; Shomoukh Alshamekh, None; Jeffrey Goldberg, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3603. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Kevin Tenerelli, Xiong Zhang, Jonathan Hertz, Praseeda Venugopalan, Catalina B. Sun, Shomoukh A. Alshamekh, Jeffrey L Goldberg; Novel transcriptional mechanisms regulate visual pathway development. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3603.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: What pathways specify retinal ganglion cell (RGC) fate in the developing retina? RGCs are born from multipotent retinal progenitor cells (RPCs) but little is known about the cell-autonomous mechanisms and environmental signals that specify RGC fate.

Methods: Using an in vitro differentiation model of RPCs, we screened and identified transcription factors important for RGC fate. Using knockout mice models, we further studied the mechanism of RGC specification in retina flat mounts by immunofluorescence and in human embryonic stem cells and induced pluripotent cell cultures assaying for RGC differentiation.

Results: We found a new molecular pathway involving Sox4/Sox11 is required for RGC differentiation from retinal progenitor cells (RPCs) and for optic nerve formation in mice in vivo, and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGC-like cells. The previously described inhibitor of RGC differentiation, REST, depended on suppression of Sox4 expression. A novel soluble regulator for RGC differentiation, TGFβ superfamily member GDF-15, acted through Sox4 to induce RGC differentiation from progenitor cells. Sox4 and Sox11 interacted such that the normal SUMOylation of Sox11, which decreased its nuclear localization and suppressed its pro-RGC activity, was decreased in the absence of Sox4, allowing Sox11 to compensate for Sox4 absence.

Conclusions: These data define novel regulatory mechanisms for this SoxC molecular network, and suggest pro-RGC molecular manipulations with potential promise for cell replacement-based therapies for glaucoma and other optic neuropathies.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×