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