Thyroid hormone signaling specifies cone subtypes in human retinal organoids

Kiara C. Eldred, Sarah E. Hadyniak, Katarzyna A. Hussey, Boris Brenerman, Pingwu Zhang, Xitiz Chamling, Valentin M. Sluch, Derek S. Welsbie, Samer Hattar, James Taylor, Karl Wahlin, Donald J Zack, Robert J. Johnston

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Abstract

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 that controls S versus 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.

Original languageEnglish (US)
Article numbereaau6348
JournalScience
Volume362
Issue number6411
DOIs
StatePublished - Oct 12 2018

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ASJC Scopus subject areas

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Cite this

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., & Johnston, R. J. (2018). Thyroid hormone signaling specifies cone subtypes in human retinal organoids. Science, 362(6411), [eaau6348]. https://doi.org/10.1126/science.aau6348