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Robert J Johnston, Kiara Eldred, Sarah Hadyniak, Katarzyna Hussey, Boris Brenerman, Ping-Wu Zhang, Xitiz Chamling, Valentin Sluch, Derek Stuart Welsbie, Samer Hattar, James Taylor, Karl J Wahlin, Donald J Zack; Thyroid hormone signaling specifies cone subtypes in human retinal organoids. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6405.
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© ARVO (1962-2015); The Authors (2016-present)
The mechanisms underlying specification of neuronal subtypes within the human nervous system are largely unknown. The blue/S, green/M and red/L cones of the retina enable high-acuity daytime and color vision.
To determine the mechanism controlling S vs. L/M fates, we studied the differentiation of human retinal organoids.
Organoids and retinas have similar distributions, expression profiles, and morphologies of cone subtypes. S cones are specified first, followed by L/M cones, and thyroid hormone signaling controls this temporal switch. Dynamic expression of thyroid hormone-degrading and activating proteins within the retina ensures low signaling early to specify S cones and high signaling late to produce L/M cones.
This work establishes organoids as a model for determining mechanisms of human development with promising utility for therapeutics and vision repair.Eldred, K.C., Hadyniak, S.E., Hussey, K.A., Brenerman, B., Zhang, P., Chamling, X., Sluch, V.M., Welsbie, D.S., Hattar, S., Taylor, J., Wahlin, K., Zack, D.J., and Johnston, R.J., Jr. (2018) Thyroid hormone signaling specifies cone subtypes in human retinal organoids.Science, 362, 6411.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Day 361 human retinal organoid. Blue = blue opsin; green = red/green opsin; red = rhodopsin.
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