4.5 Review

Thyroid hormone regulators in human cerebral cortex development

Journal

JOURNAL OF ENDOCRINOLOGY
Volume 255, Issue 3, Pages R27-R36

Publisher

BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-22-0189

Keywords

neocortex; transcriptome; thyroid hormones

Funding

  1. Programa Estatal de Investigacion
  2. Desarrollo e Innovacion Orientada a los Retos de la Sociedad
  3. Center for Biomedical Research on Rare Diseases
  4. Instituto de Salud Carlos III

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This article reviews the role of thyroid hormones in human neocortex development, focusing on the expression of thyroid hormone regulators in specific cells. Recent advances in single-cell transcriptomic approaches allow for the profiling of thyroid hormone transporters, deiodinases, and receptors in developing human neocortex.
Brain development is critically dependent on the timely supply of thyroid hormones. The thyroid hormone transporters are central to the action of thyroid hormones in the brain, facilitating their passage through the blood-brain barrier. Mutations of the monocarboxylate transporter 8 (MCT8) cause the Allan-Herndon-Dudley syndrome, with altered thyroid hormone concentrations in the blood and profound neurological impairment and intellectual deficit. Mouse disease models have revealed interplay between transport, deiodination, and availability of T3 to receptors in specific cells. However, the mouse models are not satisfactory, given the fundamental differences between the mouse and human brains. The goal of the present work is to review human neocortex development in the context of thyroid pathophysiology. Recent developments in single-cell transcriptomic approaches aimed at the human brain make it possible to profile the expression of thyroid hormone regulators in single-cell RNA-Seq datasets of the developing human neocortex. The data provide novel insights into the specific cellular expression of thyroid hormone transporters, deiodinases, and receptors.

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