Journal article
Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development
The Journal of neuroscience, Vol.37(19), pp.4967-4981
05/10/2017
DOI: 10.1523/JNEUROSCI.3430-13.2017
PMCID: PMC5426184
PMID: 28411269
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
, 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.
Glaucoma is the most common cause of blindness worldwide and, along with other optic neuropathies, is characterized by loss of retinal ganglion cells (RGCs). Unfortunately, vision and RGC loss are irreversible, and lead to bilateral blindness in ∼14% of all diagnosed patients. Differentiated and transplanted RGC-like cells derived from stem cells have the potential to replace neurons that have already been lost and thereby to restore visual function. These data uncover new mechanisms of retinal progenitor cell (RPC)-to-RGC and human stem cell-to-RGC fate specification, and take a significant step toward understanding neuronal and retinal development and ultimately cell-transplant therapy.
Details
- Title: Subtitle
- Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development
- Creators
- Kun-Che Chang - Department of Ophthalmology, Stanford University, Palo Alto, California 94304, kunche@stanford.eduJonathan Hertz - Neuroscience Graduate ProgramXiong Zhang - Shiley Eye Center, University of California, San Diego, La Jolla, California 92093, andXiao-Lu Jin - Bascom Palmer Eye Institute, Interdisciplinary Stem Cell InstitutePeter Shaw - Shiley Eye Center, University of California, San Diego, La Jolla, California 92093, andBrooke A Derosa - Hussman Institute for Human GenomicsJanet Y Li - Bascom Palmer Eye Institute, Interdisciplinary Stem Cell InstitutePraseeda Venugopalan - Neuroscience Graduate ProgramDaniel A Valenzuela - Bascom Palmer Eye Institute, Interdisciplinary Stem Cell InstituteRoshni D Patel - Bascom Palmer Eye Institute, Interdisciplinary Stem Cell InstituteKristina R Russano - Shiley Eye Center, University of California, San Diego, La Jolla, California 92093, andShomoukh A Alshamekh - King Abdulaziz University Hospital, King Saud University, Riyadh, Saudi ArabiaCatalina Sun - Shiley Eye Center, University of California, San Diego, La Jolla, California 92093, andKevin Tenerelli - Shiley Eye Center, University of California, San Diego, La Jolla, California 92093, andChenyi Li - Shiley Eye Center, University of California, San Diego, La Jolla, California 92093, andDmitri Velmeshev - Hussman Institute for Human GenomicsYuyan Cheng - Bascom Palmer Eye Institute, Interdisciplinary Stem Cell InstituteTimothy M Boyce - Bascom Palmer Eye Institute, Interdisciplinary Stem Cell InstituteAlexandra Dreyfuss - Bascom Palmer Eye Institute, Interdisciplinary Stem Cell InstituteMohammed S Uddin - Department of Ophthalmology, Stanford University, Palo Alto, California 94304Kenneth J Muller - Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida 33136Derek M Dykxhoorn - Hussman Institute for Human GenomicsJeffrey L Goldberg - Shiley Eye Center, University of California, San Diego, La Jolla, California 92093, and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.37(19), pp.4967-4981
- DOI
- 10.1523/JNEUROSCI.3430-13.2017
- PMID
- 28411269
- PMCID
- PMC5426184
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- R01 EY025693 / NEI NIH HHS T32 NS007492 / NINDS NIH HHS T34 GM008807 / NIGMS NIH HHS
- Language
- English
- Date published
- 05/10/2017
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9984172169502771
Metrics
15 Record Views