Thyroid hormone signaling specifies cone subtypes in human retinal organoids

Science. 2018 Oct 12;362(6411):eaau6348. doi: 10.1126/science.aau6348.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Cell Line
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation, Developmental*
  • Humans
  • Mutation
  • Organoids / growth & development*
  • Organoids / metabolism
  • Proteolysis
  • Retina / cytology
  • Retina / growth & development*
  • Retinal Cone Photoreceptor Cells / classification*
  • Thyroid Hormones / metabolism*


  • Thyroid Hormones