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 T 3 with the nuclear receptors. To understand the role of thyroid hormones on cerebral cortex development, knowledge of the genes regulated by T 3 during specific stages of development is required. In our laboratory, we previously identified genes regulated by T 3 in primary cerebrocortical cells in culture. By comparing these data with transcriptomics of purified cell types from the developing cortex, the cellular targets of T 3 can be identified. In addition, many of the genes regulated transcriptionally by T 3 have defined roles in cortex development, from which the role of T 3 can be derived. This review analyzes the specific roles of T 3 -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 T 3 during the second trimester of fetal development. The main cellular targets of T 3 appear to be the Cajal-Retzius and the subplate neurons. On the other hand, T 3 regulates transcriptionally genes encoding extracellular matrix proteins, involved in cell migration and the control of diverse signaling pathways.

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

“…The hypothesis of fetal programing by maternal thyroid dysfunction via disturbed early fetal brain development and later onset of neurodevelopmental disorders appears biologically plausible, which was one of the well-known viewpoints of Sir Bradford Hill in the evaluation of a causal relationship (59 experimental studies have demonstrated developmental structural and/or functional defects after exposure to maternal thyroid dysfunction in pregnancy that may overlap with the developmental abnormalities described in neurodevelopmental disorders, and identified genes involved in the brain development that are regulated by T3 (37). Results from human observational studies are intriguing to interpret, and further studies are needed to determine and support other viewpoints of causality e.g.…”

“…Brain development is a highly regulated process and an important part of this regulation includes the coordinated and timely expression of many different genes. Thyroid hormones are important developmental factors and their crucial role in early brain development is facilitated via the regulation of gene expression (37). T3 binds to nuclear thyroid hormone receptors, and recent in vitro studies have identified genes of primary cerebrocortical cells that are regulated transcriptionally by T3 (38,39).…”

“…Focus has been on the role of epigenetic determinants (75). Thyroid hormones exert their crucial role during the fetal brain development via the regulation of gene expression (37), which indicates that epigenetic mechanisms may also be involved in fetal programing via maternal thyroid dysfunction.…”

Effect of Thyroid Hormones on Neurons and Neurodevelopment

“…In mammalian studies, also fT4 and fT3 have been detected before the initial thyroid activity, as well as early deyodinase activity and TR synthesis in CNS cells [16]. TRα1 has been localized in all CNS regions, while TRβ1 has been found selectively in the hypothalamus, the pituitary, the retina, and the cochlea, but only in later stages [17, 18].…”

Behavioral, biochemical and morphological characteristics of experimentally changed thyroid status of female mice C3H-A

“…Тирео-идные гормоны стимулируют пролиферацию и диф-ференцировку клеток мозга, экспрессию факторов роста, синтез белков внеклеточного матрикса и т. п. [12,16,17]. Поэтому изучение механизмов тиреоид-ассоциированных депрессий представляет собой актуальную задачу биологии и медицины.…”