Thyroid hormone regulated genes in cerebral cortex development

Abstract

The physiological and developmental effects of thyroid hormones are mainly due to the control of gene expression after interaction of T₃ with the nuclear receptors. To understand the role of thyroid hormones on cerebral cortex development, knowledge of the genes regulated by T₃ during specific stages of development is required. In our laboratory, we previously identified genes regulated by T₃ in primary cerebrocortical cells in culture. By comparing these data with transcriptomics of purified cell types from the developing cortex, the cellular targets of T₃ can be identified. In addition, many of the genes regulated transcriptionally by T₃ have defined roles in cortex development, from which the role of T₃ can be derived. This review analyzes the specific roles of T₃-regulated genes in the different stages of cortex development within the physiological frame of the developmental changes of thyroid hormones and receptor concentrations in the human cerebral cortex during fetal development. These data indicate an increase in the sensitivity to T₃ during the second trimester of fetal development. The main cellular targets of T₃ appear to be the Cajal-Retzius and the subplate neurons. On the other hand, T₃ regulates transcriptionally genes encoding extracellular matrix proteins, involved in cell migration and the control of diverse signaling pathways.

Keywords: brain; development; fetus; gene expression; thyroid hormone metabolism.