Thyroid Hormone Signaling Specifies Cone Subtypes in Human Retinal Organoids

Overview

Journal Science

Specialty Science

Date 2018 Oct 13

PMID 30309916

Citations 118

Authors

Kiara C Eldred

Sarah E Hadyniak

Katarzyna A Hussey

Boris Brenerman

Ping-Wu Zhang

Xitiz Chamling

Valentin M Sluch

Derek S Welsbie

Samer Hattar

James Taylor

Karl Wahlin

Donald J Zack

Robert J Johnston Jr

Affiliations

Soon will be listed here.

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.

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