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 (REST) in regulating RGC fate, and further describe a newly identified, Sox4-regulated SUMOylation site 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.SIGNIFICANCE STATEMENTGlaucoma 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 around 14% of all diagnosed patients. Differentiating and transplanting RGC-like cells derived from stem cells have the potential to replace neurons that have already been lost and thereby restore visual function. These data uncover new mechanisms of retinal progenitor cell (RPC)- and human stem cell-to-RGC fate specification, and take a significant step towards understanding neuronal and retinal development and ultimately cell transplant therapy.
Pharmacology, Toxicology and Pharmaceutical Science
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Other
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Unknown
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 September 2017.
All research outputs
#21,307,850
of 33,992,632 outputs
Outputs from Journal of Neuroscience
#16,254
of 23,202 outputs
Outputs of similar age
#200,144
of 352,287 outputs
Outputs of similar age from Journal of Neuroscience
#164
of 250 outputs
Altmetric has tracked 33,992,632 research outputs across all sources so far. This one is in the 36th percentile – i.e., 36% of other outputs scored the same or lower than it.
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