Thyroid hormones influence brain development through the regulation of gene expression.
Ca2+-dependent gene expression is a major pathway controlled by the Ca2+/calmodulin-dependent
protein kinase IV (CaMKIV), which in turn is induced by the thyroid hormone T3, as also demonstrated
in a mouse embryonic stem cell line. In addition, T3 controls the expression of
neurexin, synaptotagmin2 (SYT2), synaptotagmin-related gene1 (SRG1), and a number of other
genes involved in neurotransmitter release in a Ca2+-dependent manner. It has been noticed that the
development of dopaminergic neurons by evoking significant calcium entry occurs through TRPC
calcium channels. It was also demonstrated that the T3-mediated development of an early neuronal
network is characteristic for depolarizing GABAergic neurons concomitant with intracellular calcium
transients. An important aspect of T3-dependent regulation of gene expression in the developing
brain is its modulation by the transcription activator COUP-TF1. Regulation of alternative splicing
by CaMKIV is another important aspect for embryonal neural development since it can lead to
the expression of PMCA1a, the neuronal-specific isoform of the plasma membrane calcium pump.
Maternal hypothyroidism or CaMKIV deficiency can have a severe influence on fetal brain development.
Keywords: Thyroid hormone, CaMKIV, Neurexin, SYT2, SRG1, PMCA1a, TRPC1, COUP-TF1, Brain development, Embryonal
stem cells, Hypothyroidism.
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