Thyroid hormone regulators in human cerebral cortex development

Abstract

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 b arrier. 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 r evealed interplay between transport, deiodination, and availability of T3 to rece ptors in specific cells. However, the mouse models are not satisfactory, given the funda mental 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-c ell RNA-Seq datasets of the developing human neocortex. The data provide novel insig hts into the specific cellular expression of thyroid hormone transporters, deiodinases, and receptors.