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Thyroid hormone signaling specifies cone subtypes in human retinal organoids.
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.
Afiliação
  • Eldred KC; Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
  • Hadyniak SE; Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
  • Hussey KA; Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
  • Brenerman B; Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
  • Zhang PW; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Chamling X; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Sluch VM; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Welsbie DS; Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Hattar S; National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
  • Taylor J; Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
  • Wahlin K; Department of Computer Science, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
  • Zack DJ; Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Johnston RJ; Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Science ; 362(6411)2018 10 12.
Article em En | MEDLINE | ID: mdl-30309916
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Retina / Hormônios Tireóideos / Organoides / Células Fotorreceptoras Retinianas Cones / Regulação da Expressão Gênica no Desenvolvimento Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Retina / Hormônios Tireóideos / Organoides / Células Fotorreceptoras Retinianas Cones / Regulação da Expressão Gênica no Desenvolvimento Idioma: En Ano de publicação: 2018 Tipo de documento: Article